Benzenesulfonyl chloride → (2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carbonitrile
Reaction equation
[F:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:10])[CH2:8][OH:9])[C@H:4]([C:11]([NH2:13])=O)[CH2:3]1.Cl.CN(C)C.[C:19]1([S:25](Cl)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(#N)C.O.C(N(CC)CC)C>[C:19]1([S:25]([O:9][CH2:8][C:7]([N:5]2[CH2:6][C@@H:2]([F:1])[CH2:3][C@H:4]2[C:11]#[N:13])=[O:10])(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
(2S,4S)-4-fluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carboxa mide (381 mg) and trimethylamine hydrochloride (191 mg) were suspended in acetonitrile (10 mL) and triethylamine (1.20 mL) was added to the suspension. While this mixture was cooled in a salt-ice bath, benzenesulfonyl chloride (0.28 mL) was added dropwise. The mixture was stirred at the same temperature for 1 hour and trifluoroacetic anhydride (0.34 mL) was added dropwise. The mixture was further stirred for 1 hour. Subsequently, water (10 mL) was added to the reaction mixture and acetonitrile was evaporated under reduced pressure. The resulting crystal was collected by filtration, resuspended in diethylether (10 mL) and collected again by filtration. The collected crystal was dried under reduced pressure to give (2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carbonitrile as a white crystal (472 mg, 75% yield). This compound was identical to the compound obtained in Example 3.
Workup
- temperatureWhile this mixture was cooled in a salt-ice bath
- stirringThe mixture was further stirred for 1 hour
- customwas evaporated under reduced pressure
- filtrationThe resulting crystal was collected by filtration
- filtrationcollected again by filtration
- customThe collected crystal was dried under reduced pressure
Sources & evidence
- ORD record
- ord-189cf843759b4b77a8c44e004d4d242e
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07915427B2
Reaction notes
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