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

HRID 589628

반응식

HRID 589628 반응식
[N+:1]([CH3:4])([O-:3])=[O:2].[C:5]([O:9][C:10](=[O:34])[C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:32])/[CH:18]=[C:19](\[C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)/[C:20]([F:23])([F:22])[F:21])=[CH:13][C:12]=1[CH3:33])([CH3:8])([CH3:7])[CH3:6]>O>[C:5]([O:9][C:10](=[O:34])[C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:32])[CH2:18][C@@:19]([C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)([CH2:4][N+:1]([O-:3])=[O:2])[C:20]([F:22])([F:21])[F:23])=[CH:13][C:12]=1[CH3:33])([CH3:8])([CH3:7])[CH3:6]

참가 물질

4

반응물 2

HCID 6375NitromethaneHCID 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 ester

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
50 °C

실험 절차

Alternatively, to a solution of 1-cyclohexyl-3-[(S)-(6-methoxy-4-quinolyl)-[(1S,2S,5S)-5-vinylquinuclidin-2-yl]methyl]thiourea (10 mg, prepared according to the literature: Journal of Organic Chemistry 2008, 3475) and nitromethane (0.6 ml) under argon, was added 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (100 mg). The solution was heated for 8 days at 50° C. then allowed to stand at room temperature for 14 days. Water was then added and the resulting mixture was extracted with diethyl ether 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 (28 mg). Chiral HPLC analysis (Chiralpack IA, Heptane:2-propanol=90:10, 1 ml/min, retention time 6.06 minutes (major enantiomer), 7.19 minutes (minor enantiomer) indicated that the reaction proceeded with 89% enantioselectivity in favor of the R enantiomer.

후처리

  1. extractionthe resulting mixture was extracted with diethyl ether
  2. dry with materialthe combined organic fractions were dried over sodium sulfate
  3. customThe crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-bbc5c487f439411ba61b6633fd1f48fd
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233920B2

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