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【结 构 式】 
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【分子编号】43504 【品名】benzyl (2S)-2-[[(trifluoromethyl)sulfonyl]oxy]propanoate 【CA登记号】 |
【 分 子 式 】C11H11F3O5S 【 分 子 量 】312.2665496 【元素组成】C 42.31% H 3.55% F 18.25% O 25.62% S 10.27% |
合成路线1
该中间体在本合成路线中的序号：(IX)Treatment of 4-nitrophenol (I) with propyl iodide derivative (II) and K2CO3 in DMF, followed by reduction with hydrazine hydrate, FeCl3 and activated carbon affords (III). Conversion of aniline derivative (III) into phenylcarbamate (IV) by means of PhOCOCl and treatment of (IV) with hydrazine hydrate yields semicarbazide (V), which is then subjected to cyclization with formamidine (VI) to give triazolone derivative (VII). Benzyl (S)-lactate (VIII) is converted to triflate (IX) by means of Tf2O in the presence of DIEA and its reaction with triazolone (VII) and NaH in DMF provides derivative (X). Debenzylation of (X) by hydrogenolysis over Pd/C followed by treatment with oxalyl chloride in CH2Cl2/DMF furnishes chloride (XI), which reacts with 1,3-difluorobenzene (XII) in CH2Cl2 in the presence of AlCl3 to yield intermediate (XIII).
| 【1】 Tamura, N.; Okonogi, K.; Hayashi, R.; Matsushita, Y.; Kitazaki, T.; Tasaka, A.; Itoh, K.; Optically active antifungal azoles.VI. Synthesis and antifungal activity of N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones. Chem Pharm Bull 1996, 44, 2, 314. |
| 【2】 Kitazaki, T.; et al.; Optically active antifungal azoles. IX. An alternative synthetic route for 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone and its analogs. Chem Pharm Bull 1999, 47, 3, 360. |
| 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) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (II) | 43498 | 1,1,2,2-tetrafluoro-1-iodopropane | C3H3F4I | 详情 | 详情 | |
| (III) | 43499 | 4-(2,2,3,3-tetrafluoropropoxy)phenylamine; 4-(2,2,3,3-tetrafluoropropoxy)aniline | C9H9F4NO | 详情 | 详情 | |
| (IV) | 43500 | phenyl 4-(2,2,3,3-tetrafluoropropoxy)phenylcarbamate | C16H13F4NO3 | 详情 | 详情 | |
| (V) | 43501 | N-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-1-hydrazinecarboxamide | C10H11F4N3O2 | 详情 | 详情 | |
| (VI) | 15369 | Iminoformamide; Methanimidamide | 463-52-5 | CH4N2 | 详情 | 详情 |
| (VII) | 43502 | 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C11H9F4N3O2 | 详情 | 详情 | |
| (VIII) | 43503 | benzyl (2S)-2-hydroxypropanoate | 56777-24-3 | C10H12O3 | 详情 | 详情 |
| (IX) | 43504 | benzyl (2S)-2-[[(trifluoromethyl)sulfonyl]oxy]propanoate | C11H11F3O5S | 详情 | 详情 | |
| (X) | 43505 | benzyl (2R)-2-[5-oxo-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate | C21H19F4N3O4 | 详情 | 详情 | |
| (XI) | 43506 | (2R)-2-[5-oxo-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoyl chloride | C14H12ClF4N3O3 | 详情 | 详情 | |
| (XII) | 13095 | m-Difluorobenzene; 1,3-Difluorobenzene | 372-18-9 | C6H4F2 | 详情 | 详情 |
| (XIII) | 43507 | 2-[(1R)-2-(2,4-difluorophenyl)-1-methyl-2-oxoethyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C20H15F6N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)An alternative, stereoselective synthesis has been reported. The alkylation of the chiral N-acyl oxazolidinone (I) with benzyl L-2-[(trifluoromethylsulfonyl)oxy]propionate (II) leads to the succinic acid derivative (III). After hydrogenolysis of the benzyl ester group of (III), the resultant carboxylic acid (IV) is esterified with isobutylene and H2SO4 to afford the tert-butyl ester (V). Removal of the chiral auxiliary group of (V) is then effected by hydrolysis with lithium peroxide, yielding acid (VI). Subsequent coupling of (VI) with L-phenylglycine-N-methylamide (VII) provides diamide (VIII). Acidic tert-butyl ester cleavage in (VIII) gives acid (IX), which is condensed with O-benzyl hydroxylamine to furnish hydroxamate (X). The O-benzyl group of (X) is finally removed by catalytic hydrogenolysis over Pd/C.
| 【1】 Hirayama, R.; et al.; Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors. Bioorg Med Chem 1997, 5, 4, 765. |
| 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) | 25391 | (4S)-4-benzyl-3-(4-methylpentanoyl)-1,3-oxazolidin-2-one | C16H21NO3 | 详情 | 详情 | |
| (II) | 43504 | benzyl (2S)-2-[[(trifluoromethyl)sulfonyl]oxy]propanoate | C11H11F3O5S | 详情 | 详情 | |
| (III) | 57005 | benzyl (2S,3R)-3-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-2,5-dimethylhexanoate | C26H31NO5 | 详情 | 详情 | |
| (IV) | 57006 | (2S,3R)-3-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-2,5-dimethylhexanoic acid | C19H25NO5 | 详情 | 详情 | |
| (V) | 57007 | tert-butyl (2S,3R)-3-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-2,5-dimethylhexanoate | C23H33NO5 | 详情 | 详情 | |
| (VI) | 57008 | (2R)-2-[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]-4-methylpentanoic acid | C13H24O4 | 详情 | 详情 | |
| (VII) | 57000 | (2S)-2-amino-N-methyl-2-phenylethanamide | C9H12N2O | 详情 | 详情 | |
| (VIII) | 57009 | tert-butyl (2S,3R)-2,5-dimethyl-3-({[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]amino}carbonyl)hexanoate | C22H34N2O4 | 详情 | 详情 | |
| (IX) | 57010 | (2S,3R)-2,5-dimethyl-3-({[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]amino}carbonyl)hexanoic acid | C18H26N2O4 | 详情 | 详情 | |
| (X) | 57004 | (2R)-N~4~-(benzyloxy)-2-isobutyl-N~1~-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]-3-methylenebutanediamide | C25H31N3O4 | 详情 | 详情 |