Dimethylformamide → (2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile

HRID 501352Notes

Reaction equation

HRID 501352 reaction equation
N1CCC[C@H]1C(N)=O.C(N(CC)CC)C.ClCC(Cl)=O.[Cl:21][CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[C:30]([NH2:32])=O)=[O:24].CN(C=O)C.S(Cl)(Cl)=O>C(Cl)Cl>[Cl:21][CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[C:30]#[N:32])=[O:24]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 111306L-ProlinamideHCID 11816344(S)-1-(2-Chloroacetyl)pyrrolidine-2-carboxamide

Product 1

HCID 11073883(2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

This example was run in an analogous manner as example 1 but starting from 20.0 g (175.2 mmol) of L-Prolinamide (1), 20.5 g (201 mmol) of triethylamine, 23.2 g (203 mmol) of chloroactylchloride and totally 112 mL of methylenechloride. The resulting (S)-1-(2-Chloro-acetyl)-pyrrolidine-2-carboxylic acid amide was dehydrated while adding a solution of the Vilsmeier-Reagent at RT that was prepared from 33.8 mL (438 mmol) of DMF, 20 mL of methylenechloride and 25.3 g (201 mmol) of thionylchloride. The resulting mixture was stirred for 90 min, then quenched with water and extracted in an analogous manner as example 1. Crystallization from Isopropanol/n-heptane and drying afforded 24.7 g of (S)-1-(2-Chloroacetyl)-pyrrolidine-2-carbonitrile. (Yield: 82%, assay: 99.9% (m/m) based on HPLC).

Workup

  1. additionwhile adding a solution of the Vilsmeier-Reagent at RT that
  2. customquenched with water
  3. extractionextracted in an analogous manner as example 1
  4. customCrystallization from Isopropanol/n-heptane
  5. customdrying

Sources & evidence

ORD record
ord-b87e5160446a4d44833bde7430e13193
Source dataset
uspto-grants-2010_08
Patent number
US07772264B2

Reaction notes

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