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

HRID 589635

反応式

HRID 589635 の反応式
[C-]#N.[K+].CC(C)(O)[C:6]#[N:7].[C:10]([O:14][C:15](=[O:39])[C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:37])/[CH:23]=[C:24](\[C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=2)/[C:25]([F:28])([F:27])[F:26])=[CH:18][C:17]=1[CH3:38])([CH3:13])([CH3:12])[CH3:11].O>C1(C)C=CC=CC=1>[C:10]([O:14][C:15](=[O:39])[C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:37])[CH2:23][C@:24]([C:6]#[N:7])([C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=2)[C:25]([F:26])([F:28])[F:27])=[CH:18][C:17]=1[CH3:38])([CH3:13])([CH3:12])[CH3:11]

参加物

6

反応物 4

HCID 962WaterHCID 6406Acetone CyanohydrinHCID 9032Potassium CyanideHCID 866959924-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester

生成物 1

HCID 547617414-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester収率 70.5%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
45 °C

実験手順

Potassium cyanide (0.0090 g, 0.138 mmol) and acetone cyanohydrin (0.040 ml, 0.435 mmol) were added to a solution of 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (0.0645 g, 0.140 mmol) in toluene (1.0 ml). To this vigorously stirred suspension was added 2,3,4,5,6-pentafluorophenyl-methyl quininium chloride (0.015 g, 0.028 mmol). The reaction mixture was stirred at 45° C. for 18 hours. At this time water was added and the reaction mixture was extracted with dichloromethane (3×). The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.048 g, 66%) as a white foam. Chiral HPLC analysis (Chiralpack IA, Heptane:2-propanol:diethylamine=95:5:0.1, 1 ml/min, retention time 6.52 minutes (major enantiomer), 6.02 minutes (minor enantiomer) indicated that the reaction proceeded with 88% enantioselectivity. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, 1H), 7.78-7.72 (m, 2H), 7.48 (s, 2H), 7.46-7.42 (m, 1H), 4.17 (d, 1H), 4.02 (d, 2H), 2.62 (s, 3H), 1.62 (s, 9H)

後処理

  1. additionTo this vigorously stirred suspension was added 2,3,4,5,6-pentafluorophenyl-methyl quininium chloride (0.015 g, 0.028 mmol)
  2. extractionthe reaction mixture was extracted with dichloromethane (3×)
  3. customThe crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-910bc887c7474de1a25b01001eb32951
出典データセット
uspto-grants-2016_01
特許番号
US09233920B2

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