Imidazole → (2S,5R)-1-(2-chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile

HRID 475350Notes

Reaction equation

HRID 475350 reaction equation
[Cl:1][CH2:2][C:3]([N:5]1[C@@H:12]([C:13]#[CH:14])[CH2:11][CH2:10][C@H:6]1[C:7]([NH2:9])=O)=[O:4].N1C=CN=C1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[Cl:1][CH2:2][C:3]([N:5]1[C@@H:12]([C:13]#[CH:14])[CH2:11][CH2:10][C@H:6]1[C:7]#[N:9])=[O:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24813Phosphorus oxychlorideHCID 45081097(5R)-1-(chloroacetyl)-5-ethynyl-L-prolinamide

Product 1

HCID 16090854(2S,5R)-1-(2-chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred solution of (5R)-1-(chloroacetyl)-5-ethynyl-L-prolinamide (0.16 g, 0.745 mmol) and imidazole (0.05 g, 0.745 mmol) in dry pyridine (4 mL) at −35° C. under nitrogen was added POCl3 (0.15 mL, 1.49 mmol) dropwise. The reaction mixture was stirred between −35° C. to −15° C. for 1 hour and evaporated. The residue was diluted with dichloromethane and washed with H2O (2×), dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash chromatography (10% ethyl acetate/hexane) provided the titled compound. MS (CI) m/z 197 (M+1)+.

Workup

  1. customevaporated
  2. additionThe residue was diluted with dichloromethane
  3. washwashed with H2O (2×)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-16babfd413a04f1db1e038a033dfc67a
Source dataset
uspto-grants-2014_01
Patent number
US08637546B2

Reaction notes

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