Benzenesulfonyl chloride → (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide

HRID 606720Notes

Reaction equation

HRID 606720 reaction equation
[F:1][C:2]1([F:14])[CH2:6][N:5]([C:7](=[O:10])[CH2:8][OH:9])[C@H:4]([C:11]([NH2:13])=[O:12])[CH2:3]1.CN(C)CCCN(C)C.C(N(CC)CC)C.[C:31]1([S:37](Cl)(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(#N)C.[Cl-].[Na+].O.C(OCC)(=O)C>[C:31]1([S:37]([O:9][CH2:8][C:7]([N:5]2[CH2:6][C:2]([F:1])([F:14])[CH2:3][C@H:4]2[C:11]([NH2:13])=[O:12])=[O:10])(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8084N,N,N',N'-Tetramethyl-1,3-diaminopropaneHCID 8471TriethylamineHCID 67053337(2S)-4,4-difluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carbox amide

Product 1

HCID 24781878(2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

(2S)-4,4-difluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carbox amide (1.66 g) was suspended in acetonitrile (40 mL). To this suspension, N,N,N′,N′-tetramethyl-1,3-propanediamine (133 μL) and triethylamine (2.20 mL) were added. While the mixture was cooled in a salt-ice bath, benzenesulfonyl chloride (1.20 mL) was added dropwise. The reaction mixture was then stirred at the same temperature for 1 hour, followed by the addition of saturated brine (20 mL) and extraction with ethyl acetate (2×80 mL). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To the resulting residue, a mixture of ethyl acetate and methanol (20:1, 30 mL) was added and the resulting crystal was collected by filtration to give (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide as a white crystal (1.60 g). The filtrate was concentrated under reduced pressure and the residue was purified on a silica gel column (ethyl acetate:methanol=20:1) to give additional (2S)-1-[2-(benzenesulfonyloxy)acetyl]-4,4-difluoropyrrolidine-2-carboxamide (0.58 g). The total amount of the product was 2.18 g (79% yield).

Workup

  1. temperatureWhile the mixture was cooled in a salt-ice bath
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionTo the resulting residue, a mixture of ethyl acetate and methanol (20:1, 30 mL)
  5. additionwas added
  6. filtrationthe resulting crystal was collected by filtration

Sources & evidence

ORD record
ord-14e4097d80c84cccb2d0e2d161f17f1b
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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