Water → 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester

HRID 589629

반응식

HRID 589629 반응식
[C:1]([O:5][C:6](=[O:30])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:28])/[CH:14]=[C:15](\[C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)/[C:16]([F:19])([F:18])[F:17])=[CH:9][C:8]=1[CH3:29])([CH3:4])([CH3:3])[CH3:2].[N+:31]([CH3:34])([O-:33])=[O:32].C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:30])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:28])[CH2:14][C@@:15]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)([CH2:34][N+:31]([O-:33])=[O:32])[C:16]([F:17])([F:19])[F:18])=[CH:9][C:8]=1[CH3:29])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 962WaterHCID 6375NitromethaneHCID 11430Potassium CarbonateHCID 866959924-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester

생성물 1

HCID 547615654-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester수율 60%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
50 °C

실험 절차

Alternatively, 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (0.075 g, 0.163 mmol) and antracen-9-yl-methyl quininium bromide (0.020 g, 0.034 mmol) were dissolved in toluene (2.0 ml). Nitromethane (10 molar equivalents) and potassium carbonate (0.025 g, 0.181 mmol) were added and the resulting suspension was stirred at 50° C. for 24 h. The reaction mixture was cooled to room temperature and water was added. The resulting mixture was extracted with dichloromethane (3×) and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.051 g, 60%) as a white foam. Chiral HPLC analysis (Chiralpack AS-RH, Heptane/2-propanol=90:10, 1 ml/min, retention time 6.13 minutes (major enantiomer), 7.35 minutes (minor enantiomer)) indicated that the reaction proceeded with 62% enantioselectivity.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe resulting mixture was extracted with dichloromethane (3×)
  3. dry with materialthe combined organic fractions were dried over sodium sulfate
  4. customThe crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-5fca0dc66ecb47a79a3d55cbd83af659
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233920B2

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