Imidazole → (2S,5R)-1-(Chloroacetyl)-5-(prop-1-yn-1-yl)pyrrolidine-2-carbonitrile

HRID 855878Notes

Reaction equation

HRID 855878 reaction equation
[Cl:1][CH2:2][C:3]([N:5]1[C@@H:12]([C:13]#[C:14][CH3:15])[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]#[C:14][CH3:15])[CH2:11][CH2:10][C@H:6]1[C:7]#[N:9])=[O:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24813Phosphorus oxychlorideHCID 66756603(5R)-1-(Chloroacetyl)-5-prop-1-yn-1-yl-L-prolinamide

Product 1

HCID 16090855(2S,5R)-1-(Chloroacetyl)-5-(prop-1-yn-1-yl)pyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred solution of (5R)-1-(chloroacetyl)-5-propynyl-L-prolinamide (0.28 g, 1.23 mmol) and imidazole (0.084 g, 1.23 mmol) in dry pyridine (6 mL) at −35° C. under nitrogen was added POCl3 (0.23 mL, 2.46 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 (DCI) m/z 211 (M+H)+.

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-1b6e8d0942864a50b74f59b1b482c2bd
Source dataset
uspto-grants-2007_08
Patent number
US07262207B2

Reaction notes

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