Water → HCID 86696000, compound

HRID 589641Notes

Reaction equation

HRID 589641 reaction equation
[C-]#N.[K+].CC(C)(O)[C:6]#[N:7].[Cl:10][C:11]1[CH:12]=[C:13](/[C:18](/[C:41]([F:44])([F:43])[F:42])=[CH:19]\[C:20]([C:22]2[CH:39]=[CH:38][C:25]([C:26]([NH:28][CH2:29][C:30](=[O:37])[NH:31][CH2:32][C:33]([F:36])([F:35])[F:34])=[O:27])=[C:24]([CH3:40])[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:12]=[C:11]([Cl:10])[CH:16]=[C:15]([Cl:17])[CH:14]=1)([C:41]([F:44])([F:42])[F:43])[CH2:19][C:20]([C:22]1[CH:39]=[CH:38][C:25]([C:26]([NH:28][CH2:29][C:30](=[O:37])[NH:31][CH2:32][C:33]([F:35])([F:36])[F:34])=[O:27])=[C:24]([CH3:40])[CH:23]=1)=[O:21])#[N:7]

Participants

6

Reactant 4

HCID 962WaterHCID 6406Acetone CyanohydrinHCID 9032Potassium CyanideHCID 86696001HCID 86696001, compound

Product 1

HCID 86696000HCID 86696000, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Potassium cyanide (0.0082 g, 0.125 mmol) and acetone cyanohydrin (0.031 ml, 0.336 mmol) were added to a solution of 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide (0.0600 g, 0.111 mmol) in toluene (3.0 ml). To this vigorously stirred suspension was added antracen-9-yl-methyl quininium chloride (0.0153 g, 0.028 mmol). The reaction mixture was stirred at 90 C for 4 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-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide (0.020 g, 32%) as a light yellow solid. Chiral HPLC analysis (Chiralpack AS-RH, acetonitrile:water:methanol=45:5:50, 1 ml/min, retention time 8.70 minutes (major enantiomer), 11.30 minutes (minor enantiomer) indicated that the reaction proceeded with 94% enantioselectivity.

Workup

  1. additionTo this vigorously stirred suspension was added antracen-9-yl-methyl quininium chloride (0.0153 g, 0.028 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-4a08d83897714cf4ab5c71b8beaf0d39
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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