Water → (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carbonitrile

HRID 606724Notes

Reaction equation

HRID 606724 reaction equation
[C:1]1([S:7]([O:10][CH2:11][C:12]([N:14]2[CH2:18][C:17]([F:20])([F:19])[CH2:16][C@H:15]2[C:21]([NH2:23])=O)=[O:13])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>C(#N)C.C(OCC)(=O)C>[C:1]1([S:7]([O:10][CH2:11][C:12]([N:14]2[CH2:18][C:17]([F:20])([F:19])[CH2:16][C@H:15]2[C:21]#[N:23])=[O:13])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 24781878(2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide

Product 1

HCID 24781879(2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carbonitrileYield 96%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

(2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrroli dine-2-carboxamide (872 mg) was dissolved in acetonitrile (16 mL), followed by triethylamine (1.05 mL). While this mixture was cooled in a salt-ice bath, trifluoroacetic anhydride (0.53 mL) was added dropwise. The mixture was stirred at the same temperature for 1 hour, followed by the addition of water (16 mL) and extraction with ethyl acetate (2×60 mL). The ethyl acetate extracts were combined, washed with saturated brine (2×20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:1) to give (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carbonitrile as a white crystal (789 mg, 96% yield).

Workup

  1. temperatureWhile this mixture was cooled in a salt-ice bath
  2. washwashed with saturated brine (2×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1b01ef1ba74d4163b1d092f1cf0e6c32
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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