Methyl fluoroacetate → (S)-2-fluoro-N-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetamide

HRID 859213Notes

Reaction equation

HRID 859213 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)=[CH:10][CH:9]=2)[C:5](=[O:23])[CH2:4]1.C(N(C(C)C)C(C)C)C.[F:33][CH2:34][C:35](OC)=[O:36]>CN(C)C=O>[F:33][CH2:34][C:35]([NH:2][C@H:3]1[CH2:4][C:5](=[O:23])[N:6]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)=[CH:12][CH:13]=2)[CH2:7]1)=[O:36]

Participants

5

Reactant 3

HCID 9959Methyl fluoroacetateHCID 81531DiisopropylethylamineHCID 68614456(S)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride

Product 1

HCID 10021408(S)-2-fluoro-N-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetamideYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 100 mg (0.3 mmol) of (S)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride [Example 2g)] in 0.3 ml of N,N-dimethylformamide is treated successively with 100 μl (0.6 mmol) of N-ethyl-diisopropylamine and 55 μl (0.6 mmol) of methyl fluoroacetate. The resulting beige suspension is heated to 50° C. for 18 hours. For the working-up, the reaction mixture is evaporated, thereafter, the residue is dissolved in dichloromethane and the solution washed with 1 ml of hydrochloric acid (1N). The organic layer is separated, dried over sodium sulfate, and evaporated. For purification, the crude product is chromatographed on silica gel using a 98:2-mixture of dichloromethane and methanol as the eluent. There are obtained 30 mg (28% of theory) of (S)-2-fluoro-N-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetamide as a white solid. MS: m/e=378 (M+NH4)+.

Workup

  1. customthe reaction mixture is evaporated
  2. dissolutionthe residue is dissolved in dichloromethane
  3. washthe solution washed with 1 ml of hydrochloric acid (1N)
  4. customThe organic layer is separated
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customFor purification
  8. customthe crude product is chromatographed on silica gel using a 98

Sources & evidence

ORD record
ord-6bd1446c414b4eb395e0e8e97ae0fba7
Source dataset
uspto-grants-2006_12
Patent number
US07151111B2

Reaction notes

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