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【结 构 式】 
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【分子编号】40503 【品名】1-fluoronaphthalene 【CA登记号】321-38-0 |
【 分 子 式 】C10H7F 【 分 子 量 】146.1639832 【元素组成】C 82.17% H 4.83% F 13% |
合成路线1
该中间体在本合成路线中的序号：(V)Reaction of 2-acetylthiophene (I) with paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-1-propanone (II), which is enantioselectively reduced with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene to yield (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene and treated with oxalic acid.
| 【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【2】 Staszak, M.A.; Staten, G.S.; Weigel, L.O. (Eli Lilly and Company); Chiral synthesis of 1-aryl-3-aminopropan-1-ols. CA 2042346; EP 0457559; JP 1992226948 . |
| 【3】 Frazier, J.; Staszak, M.; Weigel, L.; Staten, G.; Deeter, J.; Asymmetric synthesis and absolute stereochemistry of LY248686. Tetrahedron Lett 1990, 31, 49, 7101. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 24490 | 1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene | 88-15-3 | C6H6OS | 详情 | 详情 |
| (II) | 40500 | 3-(dimethylamino)-1-(2-thienyl)-1-propanone | 13196-35-5 | C9H13NOS | 详情 | 详情 |
| (III) | 40501 | (2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol | 63957-11-9 | C19H25NO | 详情 | 详情 |
| (IV) | 40502 | (1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol | 116817-84-6 | C9H15NOS | 详情 | 详情 |
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VI) | 40504 | (3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine | 132335-46-7 | C19H21NOS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Reaction of thiophene-2-carboxylic acid (VIII) with oxalyl chloride and PPh3 gives the corresponding acyl chloride (IX), which is condensed with vinyltributylstannane, yielding 1-(2-thienyl)-2-propen-1-one (X). The addition of HCl to the double bond of (X) affords 3-chloro-1-(2-thienyl)-1-propanone (XI), which is reduced with BH3 and the chiral (R)-oxazaborolidine catalyst (XII) in THF to give (S)-3-chloro-1-(2-thienyl)-1-propanol (XIII) (4). Treatment of (XIII) with NaI in acetone affords the (S)-3-iodopropanol derivative (XIV), which is condensed with methylamine in THF to provide (S)-3-(methylamino)-1-(2-thienyl)-1-propanol (XV). Finally, this compound is condensed with 1-fluoronaphthalene (V) by means of NaH in DMA. The Friedel-Crafts condensation of thiophene (XVI) with 3-chloropropionyl chloride (XVII) by means of SnCl4 in benzene gives the previously reported 3-chloro-1-(2-thienyl)-1-propanone (XI), which is reduced with NaBH4 in ethanol to yield the racemic alcohol (XVIII). Optical resolution of (XVIII) performed by means of immobilized CALB (Novozyme 435, Novo-Nordisk A/S) affords the previously reported (S)-alcohol (XIII).
| 【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【2】 Wheeler, W.J.; Kuo, F.; An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers. J Label Compd Radiopharm 1995, 36, 3, 213. |
| 【3】 Hoff, B.H.; Liu, H.; Anthonsen, T.; Chemo-enzymatic synthesis of the antidepressant duloxetine and its enantiomer. Chirality 2000, 12, 1, 26. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VIII) | 40505 | 2-thiophenecarboxylic acid | 527-72-0 | C5H4O2S | 详情 | 详情 |
| (IX) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (X) | 40506 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (XI) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (XII) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (XIII) | 40509 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XIV) | 40510 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XV) | 40511 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | 116539-55-0 | C8H13NOS | 详情 | 详情 |
| (XVI) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (XVII) | 18936 | 3-chloropropanoyl chloride | 625-36-5 | C3H4Cl2O | 详情 | 详情 |
| (XVIII) | 40508 | 3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)The reaction of 2-acetylthiophene (I) with [14C]-paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-[3-14C]propan-1-one (II), which is enantioselectively reduced in toluene with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene to yield (S)-3-(dimethylamino)-1-(2-thienyl)-[3-14C]propan-1-ol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene.
| 【1】 Wheeler, W.J.; Kuo, F.; Approaches to an asymmetric synthesis of duloxetine, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled analogs. Synthesis and Applications of Isotopically Labelled Compounds 1994, 597-603. |
| 【2】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 24490 | 1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene | 88-15-3 | C6H6OS | 详情 | 详情 |
| (II) | 40500 | 3-(dimethylamino)-1-(2-thienyl)-1-propanone | 13196-35-5 | C9H13NOS | 详情 | 详情 |
| (III) | 40501 | (2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol | 63957-11-9 | C19H25NO | 详情 | 详情 |
| (IV) | 40502 | (1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol | 116817-84-6 | C9H15NOS | 详情 | 详情 |
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VI) | 40504 | (3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine | 132335-46-7 | C19H21NOS | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)The reaction of [carbonyl-14C]-2-acetylthiophene (I) with paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-[1-14C]propan-1-one (II), which is enantioselectively reduced with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene, yielding (S)-3-(dimethylamino)-1-(2-thienyl)[1-14C] propan-1-ol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene.
| 【1】 Wheeler, W.J.; Kuo, F.; Approaches to an asymmetric synthesis of duloxetine, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled analogs. Synthesis and Applications of Isotopically Labelled Compounds 1994, 597-603. |
| 【2】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 24490 | 1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene | 88-15-3 | C6H6OS | 详情 | 详情 |
| (II) | 40500 | 3-(dimethylamino)-1-(2-thienyl)-1-propanone | 13196-35-5 | C9H13NOS | 详情 | 详情 |
| (III) | 40501 | (2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol | 63957-11-9 | C19H25NO | 详情 | 详情 |
| (IV) | 40502 | (1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol | 116817-84-6 | C9H15NOS | 详情 | 详情 |
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VI) | 40504 | (3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine | 132335-46-7 | C19H21NOS | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)The reaction of thiophene-2-[14C]carboxylic acid (VII) with oxalyl chloride and PPh3 gives the corresponding labeled acyl chloride (VIII), which is condensed with vinyltributylstannane, yielding 1-(2-thienyl)-[1-14C]prop-2-en-1-one (IX). The addition of HCl to the double bond of (IX) affords 3-chloro-1-(2-thienyl)-[1-14C]propan-1-one (X), which is reduced with BH3 and the chiral (R)-oxazaborolidine catalyst (XI) in THF to give (S)-3-chloro-1-(2-thienyl)-[1-14C]propan-1-ol (XII). Treatment of (XII) with NaI in acetone affords the labeled (S)-3-iodopropanol derivative (XIII), which is condensed with methylamine in THF to provide (S)-3-(methylamino)-1-(2-thienyl)-[1-14C]propan-1-ol (XIV). Finally, this compound is condensed with 1-fluoronaphthalene (V) by means of NaH in DMA.
| 【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【2】 Wheeler, W.J.; Kuo, F.; An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers. J Label Compd Radiopharm 1995, 36, 3, 213. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VII) | 40505 | 2-thiophenecarboxylic acid | 527-72-0 | C5H4O2S | 详情 | 详情 |
| (VII) | 45145 | 2-thiophenecarboxylic acid | C5H4O2S | 详情 | 详情 | |
| (VIII) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (VIII) | 45146 | 2-thiophenecarbonyl chloride | C5H3ClOS | 详情 | 详情 | |
| (IX) | 40506 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (IX) | 45147 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (X) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (X) | 45148 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (XI) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (XII) | 40509 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XII) | 45149 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XIII) | 40510 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XIII) | 45150 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XIV) | 40511 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | 116539-55-0 | C8H13NOS | 详情 | 详情 |
| (XIV) | 45151 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | C8H13NOS | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(V)The enantioselective reduction of 3-chloro-1-(2-thienyl)-1-propanone (I) by means of BH3 catalyzed by (R)-1-methyl-3,3-diphenyltetrahydropyrrolo[1,2-c][1,3,2]oxazaborole (II) in THF gives 3-chloro-1-(2-thienyl)propan-1(S)-ol (III), which is treated with methylamine and NaI in acetone/THF to yield (S)-N-methyl-N-[3-(2-thienyl)propyl]amine (IV). Finally, this compound is condensed with 1-fluoronaphthalene (V) by means of NaH in DMA to provide duloxetine. Alternatively, the enantioselective reduction of 3-chloro-1-(2-thienyl)-1-propanone (I) by means of BH3 catalyzed by (S)-1-methyl-3,3-diphenyltetrahydropyrrolo[1,2-c][1,3,2]oxazaborole (VI) in THF gives 3-chloro-1-(2-thienyl)propan-1(R)-ol (VII), which is condensed with 1-naphthol (VIII) by means of DEAD and PPh3 to yield the expected aryl ether (IX), with inversion of the configuration. Finally, this compound is treated with methylamine and NaI in acetone/THF to provide duloxetine.
| 【1】 Bymaster, F.P.; Beedle, E.E.; Findlay, J.; Gallagher, P.T.; Krushinski J.H.; Mitchell, S.; Robertson, D.W.; Thompson, D.C.; Wallace, L.; Wong, D.T.; Duloxetine (Cymbalta(TM)), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg Med Chem Lett 2003, 13, 24, 4477. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (II) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (III) | 40509 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (IV) | 40511 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | 116539-55-0 | C8H13NOS | 详情 | 详情 |
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VI) | 28292 | (S)-Methyl oxazaborolidine; (3aS)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-81-8 | C18H20BNO | 详情 | 详情 |
| (VII) | 40512 | (1R)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (VIII) | 22935 | alpha-naphthol; 1-naphthol | 90-15-3 | C10H8O | 详情 | 详情 |
| (IX) | 40513 | (1S)-3-chloro-1-(2-thienyl)propyl 1-naphthyl ether; 2-[(1S)-3-chloro-1-(1-naphthyloxy)propyl]thiophene | C17H15ClOS | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VIII)In the original synthesis of the title compound, Knoevenagel condensation of benzaldehyde (I) with malonic acid (II) in the presence of ammonium acetate produced the beta-aminoacid (III). Reductive alkylation of the amino group of (III) with formaldehyde produced the dimethyl amine (IV). Then, Fischer esterification of (IV) with ethanolic HCl furnished the intermediate amino ester (V). Amino ester (V) was alternatively obtained by Michael addition of dimethylamine to ethyl cinnamate (VI). Reduction of the ester function of (V) provided amino alcohol (VII). The sodium alkoxide of (VII) was then coupled with 1-fluoronaphthalene (VIII) to produce the racemic amino ether, which was finally resolved into enantiomers by means of tartaric acid.
| 【1】 Robertson, D.W.; Thompson, D.C.; Wong, D.T. (Eli Lilly and Company); 1-Phenyl-3-naphthalenyloxypropanamines. AU 8814335; EP 0288188; JP 1988258837; US 5135947 . |
| 【2】 Wheeler, W.J.; O'Bannon, D.D.; A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer. J Label Compd Radiopharm 1992, 31, 4, 305. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (II) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
| (III) | 59224 | 3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid | 614-19-7 | C9H11NO2 | 详情 | 详情 |
| (IV) | 59221 | N,N-dimethyl-3-phenyl-beta-alanine | C11H15NO2 | 详情 | 详情 | |
| (V) | 59222 | ethyl 3-(dimethylamino)-3-phenylpropanoate | C13H19NO2 | 详情 | 详情 | |
| (VI) | 54905 | Cinnamic acid ethylester; Ethyl cinnamate | C11H12O2 | 详情 | 详情 | |
| (VII) | 59223 | 3-(dimethylamino)-3-phenyl-1-propanol | C11H17NO | 详情 | 详情 | |
| (VIII) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(VIII)An alternative synthesis starting from the chiral precursor N-Boc-(R)-phenylglycine (IX) was reported. Borane reduction of (IX) provided the N-Boc aminoalcohol (X), which was activated as the mesylate (XI) by reaction with methanesulfonyl chloride in pyridine, yielding (XI). Displacement of the mesylate group of (XI) with NaCN furnished the Boc-aminonitrile (XII). Hydrolysis of the nitrile group of (XII) with concomitant N-Boc group cleavage under acidic conditions gave aminoacid (XIII). This was reduced to amino alcohol (XIV) using borane in THF. Eschweiler-Clarke methylation of aminoalcohol (XIV) yielded the dimethyl amine (XV). This was finally condensed with 1-fluoronaphthalene (VIII) to produce the title naphthyl ether. The [14C]-labeled compound was similarly prepared employing 14C-sodium cyanide.
| 【1】 Wheeler, W.J.; O'Bannon, D.D.; A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer. J Label Compd Radiopharm 1992, 31, 4, 305. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (IX) | 22613 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoic acid | 2900-27-8 | C13H17NO4 | 详情 | 详情 |
| (X) | 59225 | (R)-N-(tert-Butoxycarbonyl)-phenylglycinol; N-t-BOC-D-phenylglycinol | 102089-74-7 | C13H19NO3 | 详情 | 详情 |
| (XI) | 59226 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-phenylethyl methanesulfonate | C14H21NO5S | 详情 | 详情 | |
| (XII) | 59227 | tert-butyl (1S)-2-cyano-1-phenylethylcarbamate | C14H18N2O2 | 详情 | 详情 | |
| (XIII) | 56272 | (3R)-3-amino-3-phenylpropanoic acid | C9H11NO2 | 详情 | 详情 | |
| (XIV) | 59228 | (R)-3-Amino-3-phenylpropan-1-ol | C9H13NO | 详情 | 详情 | |
| (XV) | 59229 | (3S)-3-(dimethylamino)-3-phenyl-1-propanol | C11H17NO | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(V)Mannich reaction of N-(2-methoxyphenyl)piperazine (I) with 3-acetylthiophene (II) in the presence of paraformaldehyde and HCl in refluxing EtOH leads to the piperazinyl propanone (III). Subsequent keto group reduction with NaBH4 gives alcohol (IV). This is then condensed with 1-fluoronaphthalene (V) in the presence of NaH to produce the title naphthyl ether.
| 【1】 Oficialdegui, A.-M.; Martínez-Esparza, J.; Pérez-Sailanes, S.; et al.; New 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives, with dual action at 5-HT1A serotonin receptors and serotonin transporter, as a new class of antidepressants. J Med Chem 2001, 44, 3, 418. |
| 【2】 Bosch Rovira, A.; Roca Acin, J.; Monge Vega, A.; Del Rio Zambrana, J.; Palop Cubillo, J.A.; Lasheras Aldaz, B.; Del Castillo Nieto, J.C. (Laboratorios Vita, SA); Cpds. derived from thiophene and benzothiophene, and related utilisation and compsn.. EP 1008594; ES 2128266; JP 2002511883; US 6262056; WO 9902516 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11882 | 1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine | 35386-24-4 | C11H16N2O | 详情 | 详情 |
| (II) | 34619 | 1-(3-thienyl)-1-ethanone | 1468-83-3 | C6H6OS | 详情 | 详情 |
| (III) | 57497 | 3-[4-(2-methoxyphenyl)-1-piperazinyl]-1-(3-thienyl)-1-propanone | C18H22N2O2S | 详情 | 详情 | |
| (IV) | 57498 | 3-[4-(2-methoxyphenyl)-1-piperazinyl]-1-(3-thienyl)-1-propanol | C18H24N2O2S | 详情 | 详情 | |
| (V) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |