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【结 构 式】 
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【分子编号】56141 【品名】(R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol 【CA登记号】16355-00-3 |
【 分 子 式 】C8H10O2 【 分 子 量 】138.1662 【元素组成】C 69.55% H 7.3% O 23.16% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 1(R)-phenylethane-1,2-diol (I) with N-hydroxyphthalimide (II) by means of DEAD and PPh3 gives the N-alcoxyphthalimide (III) with(S)-configuration. The hydrazinolysis of (III) with hydrazine hydrate affords the O-alkylhydroxylamine (IV), which is condensed with benzaldehyde (V) to provide the alkylated benzaldoxime (VI). The alkylation of the oxime (VI) with vinyl lithium (VII) in toluene gives the N, O dialkylated hydroxylamine (VIII), which is treated with Zn and AcOH to yield 1(R)-phenylallylamine (IX). The protection of the amine (IX) with Boc2O and NaOH affords the carbamate (X), which is oxidized at the vinyl double bond by means of OsO4 and NaIO4 to provide the acetaldehyde (XI). The reaction of aldehyde (XI) with allylmagnesium bromide (XII) in ethyl ether gives the aminoalcohol (XIII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (XIV).
| 【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029. |
| 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) | 56141 | (R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol | 16355-00-3 | C8H10O2 | 详情 | 详情 |
| (II) | 13505 | N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione | 524-38-9 | C8H5NO3 | 详情 | 详情 |
| (III) | 56142 | 2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione | C16H13NO4 | 详情 | 详情 | |
| (IV) | 56143 | (2S)-2-(aminooxy)-2-phenyl-1-ethanol | C8H11NO2 | 详情 | 详情 | |
| (V) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VI) | 62256 | benzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime | C15H15NO2 | 详情 | 详情 | |
| (VII) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VIII) | 62257 | (2S)-2-phenyl-2-({[(1R)-1-phenyl-2-propenyl]amino}oxy)-1-ethanol | C17H19NO2 | 详情 | 详情 | |
| (IX) | 62258 | (1R)-1-phenyl-2-propenylamine; (1R)-1-phenyl-2-propen-1-amine | C9H11N | 详情 | 详情 | |
| (X) | 62259 | tert-butyl (1R)-1-phenyl-2-propenylcarbamate | C14H19NO2 | 详情 | 详情 | |
| (XI) | 45428 | tert-butyl (1S)-2-oxo-1-phenylethylcarbamate | C13H17NO3 | 详情 | 详情 | |
| (XII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XIII) | 62260 | tert-butyl (1S)-2-hydroxy-1-phenyl-4-pentenylcarbamate | C16H23NO3 | 详情 | 详情 | |
| (XIV) | 62261 | tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate | C22H37NO3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)A new procedure for the asymmetric synthesis of amine (III) was reported. Mitsunobu coupling of N-hydroxyphthalimide (V) with the chiral auxiliary (R)-phenylglycol (IV) yielded the (S)-alkoxyphthalimide (VI). Hydrazinolysis of (VI) provided the free alkoxyamine (VII), which was condensed with 3-methoxybenzaldehyde (VIII) to afford oxime (IX). Diastereoselective addition of methyllithium to the oxime ether (IX) led to the methyl adduct (X) as the major isomer. Then, reductive N-O bond cleavage to furnish amine (III) was carried out by using zinc-acetic acid or, with an improved yield, using molybdenum hexacarbonyl.
| 【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 56140 | (R)-1-(3-Methoxyphenyl)ethylamine; (R)-3-Methoxy-alpha-methylbenzylamine; (R)-m-Methoxy-alpha-methylbenzylamine | 88196-70-7 | C9H13NO | 详情 | 详情 |
| (IV) | 56141 | (R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol | 16355-00-3 | C8H10O2 | 详情 | 详情 |
| (V) | 13505 | N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione | 524-38-9 | C8H5NO3 | 详情 | 详情 |
| (VI) | 56142 | 2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione | C16H13NO4 | 详情 | 详情 | |
| (VII) | 56143 | (2S)-2-(aminooxy)-2-phenyl-1-ethanol | C8H11NO2 | 详情 | 详情 | |
| (VIII) | 20589 | 3-methoxybenzaldehyde; m-Anisaldehyde | 591-31-1 | C8H8O2 | 详情 | 详情 |
| (IX) | 56144 | 3-methoxybenzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime | C16H17NO3 | 详情 | 详情 | |
| (X) | 56145 | (2S)-2-({[(1R)-1-(3-methoxyphenyl)ethyl]amino}oxy)-2-phenyl-1-ethanol | C17H21NO3 | 详情 | 详情 |