Methanol → HCID 57951162, compound

HRID 1919811Notes

Reaction equation

HRID 1919811 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[C:11](=[O:24])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].CO.[Cl:29][C:30]1[CH:39]=[CH:38][C:33]([C:34](OC)=[O:35])=[CH:32][CH:31]=1.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[Cl:29][C:30]1[CH:39]=[CH:38][C:33]([C:34]([CH:10]2[CH2:9][C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][C:20]([F:21])([F:22])[F:23])=[CH:17][CH:18]=3)[C:11]2=[O:24])=[O:35])=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 14307Methyl 4-chlorobenzoateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57951116HCID 57951116, compound

Product 1

HCID 57951162HCID 57951162, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add (R)-5-(3-fluoro-phenyl)-1-(4-trifluoromethoxy-phenyl)-pyrrolidin-2-one (0.89 g, 2.63 mmol) to a suspension of sodium hydride (0.61 g, 15.36 mmol) in dry toluene (40 mL) and stir at room temperature under nitrogen. Add methanol (0.29 mL, approx. 16 mmol) followed by methyl p-chlorobenzoate (1.2 g, 7.0 mmol). Heat under reflux overnight. Cool, add aqueous NH4Cl solution, extract with ethyl acetate. Collect the organic phase, dry over anhydrous magnesium sulfate, evaporate and purify on a silica gel column (isohexane-ethyl acetate) to give the titled compound (1.1 g, 88% yield) MS (m/z): 478 (M+1).

Workup

  1. temperatureHeat
  2. temperatureunder reflux overnight
  3. temperatureCool
  4. extractionextract with ethyl acetate
  5. customCollect the organic phase
  6. dry with materialdry over anhydrous magnesium sulfate
  7. customevaporate
  8. custompurify on a silica gel column (isohexane-ethyl acetate)

Sources & evidence

ORD record
ord-7977f3292444416d88e45bc2866baf54
Source dataset
uspto-grants-2012_05
Patent number
US08168659B2

Reaction notes

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