Acetyl chloride → Sembragiline

HRID 858930Notes

Reaction equation

HRID 858930 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(CC)CC)C.[C:31](Cl)(=[O:33])[CH3:32]>ClCCl>[F:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[CH2:15][O:14][C:11]1[CH:10]=[CH:9][C:8]([N:6]2[C:5](=[O:23])[CH2:4][C@H:3]([NH:2][C:31](=[O:33])[CH3:32])[CH2:7]2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 68614456(S)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride

Product 1

HCID 10246762Sembragiline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 11.3 mmol of (S)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride in 86 ml of dichloromethane was treated with 23.8 mmol of triethylamine and cooled to 0° C. To this solution, 12.5 mmol of acetylchloride were added and stirring at 0° C. was continued for 15 min. For the working-up, the reaction mixture was extracted twice with 100 ml of water. The organic layer was separated, dried over sodium sulfate and evaporated under reduced pressure. The crude product was triturated in 100 ml of toluene, then the solid collected on a filter funnel. In a second step, the product was triturated in 200 ml of tert-butylmethylether at RT. Again, the solid product was collected on a filter funnel and dried under high vacuum. There was obtained (S)-N-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetamide as a white solid. MS: m/e=343 (M+H)+; enantiomeric excess: >99.5%.

Workup

  1. extractionthe reaction mixture was extracted twice with 100 ml of water
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe crude product was triturated in 100 ml of toluene
  6. customthe solid collected on a filter funnel
  7. customIn a second step, the product was triturated in 200 ml of tert-butylmethylether at RT
  8. customAgain, the solid product was collected on a filter funnel
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-66c9a3d550e547e1ac34130df3e40877
Source dataset
uspto-grants-2006_12
Patent number
US07148362B2

Reaction notes

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