Water → HCID 86695995, compound

HRID 589637Notes

Reaction equation

HRID 589637 reaction equation
[N+:1]([CH3:4])([O-:3])=[O:2].[Cl:5][C:6]1[CH:7]=[C:8](/[C:13](/[C:30]([F:33])([F:32])[F:31])=[CH:14]\[C:15]([C:17]2[CH:18]=[CH:19][C:20]([N:25]3[CH:29]=[N:28][CH:27]=[N:26]3)=[C:21]([CH:24]=2)[C:22]#[N:23])=[O:16])[CH:9]=[C:10]([Cl:12])[CH:11]=1.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1>[Cl:5][C:6]1[CH:7]=[C:8]([C@:13]([CH2:4][N+:1]([O-:3])=[O:2])([C:30]([F:31])([F:33])[F:32])[CH2:14][C:15]([C:17]2[CH:18]=[CH:19][C:20]([N:25]3[CH:29]=[N:28][CH:27]=[N:26]3)=[C:21]([CH:24]=2)[C:22]#[N:23])=[O:16])[CH:9]=[C:10]([Cl:12])[CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6375Nitromethane2×HCID 11430Potassium CarbonateHCID 67377109HCID 67377109, compound

Product 1

HCID 86695995HCID 86695995, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of anthracenylmethyl quininium chloride (19 mg), nitromethane (0.025 ml) and 5-[(E)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-but-2-enoyl]-2-(1,2,4-triazol-1-yl)benzonitrile (100 mg) in toluene (2 mL) under argon, was heated for 2 hours at 50° C. then potassium carbonate (64 mg) was added. The reaction was heated for 24 hours at 50° C. then more nitromethane (0.02 mL) was added. The reaction was heated again at 50° C. for 3 hours then was allowed to stand at room temperature for 18 hours. Water was then added and the resulting mixture was extracted with dichloromethane and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 50% ethyl acetate in cyclohexane) to afford 5-[(3R)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl]-2-(1,2,4-triazol-1-yl)benzonitrile (69 mg). Chiral HPLC analysis (CHIRALPAK AS-RH, acetonitrile:Methanol:water=40:5:55, 1 ml/min, retention time 11.88 minutes (minor enantiomer), 13.88 minutes (major enantiomer) indicated that the reaction proceeded with 50% enantioselectivity in favor of the R enantiomer.

Workup

  1. temperatureThe reaction was heated again at 50° C. for 3 hours
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. dry with materialthe combined organic fractions were dried over sodium sulfate
  4. customThe crude product was purified by flash chromatography (0% to 50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-62de43ddf406446fb719b46fdd86bece
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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