Water → 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide

HRID 589640Notes

Reaction equation

HRID 589640 reaction equation
[C-]#N.[K+].CC(C)(O)[C:6]#[N:7].[Cl:10][C:11]1[CH:12]=[C:13](/[C:18](/[C:37]([F:40])([F:39])[F:38])=[CH:19]\[C:20]([C:22]2[CH:35]=[CH:34][C:25]([C:26]([NH:28][C:29]3([CH3:33])[CH2:32][S:31][CH2:30]3)=[O:27])=[C:24]([CH3:36])[CH:23]=2)=[O:21])[CH:14]=[C:15]([Cl:17])[CH:16]=1.O>C1(C)C=CC=CC=1>[C:6]([C@@:18]([C:13]1[CH:14]=[C:15]([Cl:17])[CH:16]=[C:11]([Cl:10])[CH:12]=1)([C:37]([F:40])([F:39])[F:38])[CH2:19][C:20]([C:22]1[CH:35]=[CH:34][C:25]([C:26]([NH:28][C:29]2([CH3:33])[CH2:32][S:31][CH2:30]2)=[O:27])=[C:24]([CH3:36])[CH:23]=1)=[O:21])#[N:7]

Participants

6

Reactant 4

HCID 962WaterHCID 6406Acetone CyanohydrinHCID 9032Potassium CyanideHCID 866959984-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide

Product 1

HCID 866959994-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamideYield 24%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Potassium cyanide (0.0090 g, 0.139 mmol) and acetone cyanohydrin (0.034 ml, 0.372 mmol) were added to a solution of 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide (0.0600 g, 0.123 mmol) in toluene (3.0 ml). To this vigorously stirred suspension was added 2,3,4,5,6-pentafluorophenyl-methyl quininium chloride (0.0180 g, 0.031 mmol). The reaction mixture was stirred at 90° C. for 6 days. After this time water was added and the reaction mixture was extracted with dichloromethane (3×). The crude product was purified by flash chromatography (0% to 25% ethyl acetate in cyclohexane) to afford 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide (0.015 g, 24%) as a light yellow solid. Chiral HPLC analysis (Chiralpack IB, Heptane:2-propanol=70:30, 1 ml/min, retention time 5.91 minutes (major enantiomer), 5.31 minutes (minor enantiomer) indicated that the reaction proceeded with 69% enantioselectivity.

Workup

  1. additionTo this vigorously stirred suspension was added 2,3,4,5,6-pentafluorophenyl-methyl quininium chloride (0.0180 g, 0.031 mmol)
  2. extractionthe reaction mixture was extracted with dichloromethane (3×)
  3. customThe crude product was purified by flash chromatography (0% to 25% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-c44735de2ce64ca0a5f814ebb622148e
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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