Pyridine → (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile

HRID 1869645Notes

Reaction equation

HRID 1869645 reaction equation
[Br:1][CH2:2][C:3](Br)=[O:4].[NH:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]#[N:12].N1C=CC=CC=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Br:1][CH2:2][C:3]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]#[N:12])=[O:4]

Participants

6

Reactant 3

HCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 5706552(2S)-pyrrolidine-2-carbonitrile

Product 1

HCID 11031276(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrileYield 82.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a cold solution (−10° C.) of bromoacetyl bromide (2.0 g, 10.0 mmol) in CH2Cl2 (30 mL), a solution of (S)-pyrrolidine-2-carbonitrile (480 mg, 5.0 mmol) and pyridine (1.4 g, 210 mmol) together with a catalytic amount of DMAP (50 mg) in CH2Cl2 (10 mL) was added over a 30 minute period. After stirring for about 10 minutes, the reaction temperature was gradually increased to room temperature. Stirring at room temperature was continued overnight. The residue was diluted with CH2Cl2 (60 mL), washed with ice water and cold 10% sodium bicarbonate aqueous solution to give crude product (1.01 g; yield of 93%). Column chromatography purification of the crude product resulted in pure 1-(2-bromo-acetyl)-(S)-pyrrolidine-2-carbonitrile (892 mg; 82.6% yield).

Workup

  1. stirringStirring at room temperature
  2. waitwas continued overnight
  3. washwashed with ice water and cold 10% sodium bicarbonate aqueous solution
  4. customto give crude product (1.01 g; yield of 93%)
  5. customColumn chromatography purification of the crude product

Sources & evidence

ORD record
ord-215d032144eb482e9e54cb7de404639e
Source dataset
uspto-grants-2009_12
Patent number
US07638638B2

Reaction notes

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