(+)-Methoxyphenylacetic acid → (2S)-methoxyphenyl acetic acid (1S)-2-(t-butoxycarbonyl-methylamino)-1-(4-fluorophenyl)ethyl ester

HRID 1351266노트

반응식

HRID 1351266 반응식
[C:1]([O:5][C:6](=[O:19])[N:7]([CH2:9][CH:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[OH:11])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][C@@H:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23](O)=[O:24].CCCCCC.C(OCC)(=O)C>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)C>[C:1]([O:5][C:6]([N:7]([CH3:8])[CH2:9][C@@H:10]([O:11][C:23](=[O:24])[C@@H:22]([O:21][CH3:20])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)=[O:19])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 3

HCID 643325(+)-Methoxyphenylacetic acidHCID 21226206Ethyl acetate hexaneHCID 69414015tert-butyl N-[2-(4-fluorophenyl)-2-hydroxyethyl]-N-methylcarbamate

생성물 1

HCID 86600988(2S)-methoxyphenyl acetic acid (1S)-2-(t-butoxycarbonyl-methylamino)-1-(4-fluorophenyl)ethyl ester

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

To a solution of [2-(4-fluorophenyl)-2-hydroxyethyl]methyl-carbamic acid t-butyl ester (the compound of Preparation Example 32) (8.46 g) and (S)-(+)-α-methoxyphenyl acetic acid (5.74 g) in dichloromethane (60 mL) was added 4-dimethylaminopyridine (0.19 g) and N,N-dicyclohexylcarbodiimide (7.7 g) on an ice bath. The solution was stirred for 3.5 hours while being slowly warmed to room temperature. When the reaction solution was developed with silica gel TLC (hexane/ethyl acetate=4:1), two products could be identified. After diluting with diethyl ether, the insoluble matter was removed by Celite filtration. The residue that was obtained upon removing the solvent by evaporation was purified by silica gel column chromatography (hexane/ethyl acetate), the (S, S) isomer (the compound that demonstrates a high Rf value in TLC) (3.60g) was obtained from the low polarity elution portion. The NMR suggested that it was a mixture of rotamers. The three-dimensional structure was determined from the NMR data by applying the Mosher method.

후처리

  1. customthe insoluble matter was removed by Celite filtration
  2. customThe residue that was obtained
  3. customupon removing the solvent
  4. customby evaporation
  5. customwas purified by silica gel column chromatography (hexane/ethyl acetate)
  6. customwas obtained from the low polarity elution portion
  7. additiona mixture of rotamers

출처 및 근거

ORD 기록
ord-e9ea71faac714e19838c884e1ce9c438
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07217723B2

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