Imidazole → (2S,5S)-1-(Chloroacetyl)-5-methylpyrrolidine-2-carbonitrile

HRID 855881Notes

Reaction equation

HRID 855881 reaction equation
[Cl:1][CH2:2][C:3]([N:5]1[C@@H:9]([CH3:10])[CH2:8][CH2:7][C@H:6]1[C:11]([NH2:13])=O)=[O:4].N1C=CN=C1.O=P(Cl)(Cl)Cl.[NH4+].[Cl-]>N1C=CC=CC=1>[Cl:1][CH2:2][C:3]([N:5]1[C@@H:9]([CH3:10])[CH2:8][CH2:7][C@H:6]1[C:11]#[N:13])=[O:4]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24813Phosphorus oxychlorideHCID 25517Ammonium ChlorideHCID 45080982(5S)-1-(Chloroacetyl)-5-methyl-L-prolinamide

Product 1

HCID 16090846(2S,5S)-1-(Chloroacetyl)-5-methylpyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-35 °C

Procedure

(2S,5S)-1-(2-Chloro-acetyl)-5-methyl-pyrrolidine-2-carboxylic acid amide (0.25 g, 1.2 mmol) and imidazole (85 mg, 1.25 mmol) ware mixed in pyridine (5 mL). The mixture was cooled to −35° C. and POCl3 (0.18 mL, 1.8 mmol) was added slowly. The mixture was stirred at −35° C. for 1 h. Saturated NH4Cl (20 mL) was added, and the mixture was extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The oil was purified by flash chromatography (hexane: EtOAc, 2:1) to yield the title compound. MS (DCI) m/z 187 (M+H)+.

Workup

  1. extractionthe mixture was extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe oil was purified by flash chromatography (hexane: EtOAc, 2:1)

Sources & evidence

ORD record
ord-9fc9c715e14b4333a967f1ff9488f83d
Source dataset
uspto-grants-2007_08
Patent number
US07262207B2

Reaction notes

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