Chloroacetyl chloride → (4R)-3-(chloroacetyl)-1,3-thiazolidine-4-carbonitrile

HRID 22936Notes

Reaction equation

HRID 22936 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].Cl.[NH:7]1[CH2:14][S:13][CH2:12][C@H:8]1[C:9]([NH2:11])=[O:10].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1.ClCCl.C(N(CC)CC)C>[ClH:1].[NH:7]1[CH2:14][S:13][CH2:12][C@H:8]1[C:9]([NH2:11])=[O:10].[Cl:1][CH2:2][C:3]([N:7]1[C@H:8]([C:9]#[N:11])[CH2:12][S:13][CH2:14]1)=[O:4]

Participants

8

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 9845Trifluoroacetic anhydrideHCID 66879498HCID 66879498, compound

Product 2

HCID 55265408(4R)-3-(chloroacetyl)-1,3-thiazolidine-4-carbonitrileHCID 66879498HCID 66879498, compound

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

L-thioprolineamide hydrochloride was synthesized according to the process described in the literature (Ashworth et. al., Bioorg. Med. Chem. Lett., Vol. 6, pp. 2745-2748, 1996). 2.36 ml of chloroacetyl chloride was added to a solution of 150 ml of dichloromethane containing 5.00 g of L-thioprolineamide hydrochloride thus obtained and 8.67 ml of triethylamine under ice-cooling, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture was added a dichloromethane solution containing 4.8 ml of pyridine and 8.4 ml of trifluoroacetic anhydride, and the mixture was further stirred at room temperature for 1 hour. The reaction mixture was washed with an aqueous 10% HCl solution and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, and subsequently, the residue was crystallized from ether to obtain 4.82 g of (R)-3-chloroacetyl-4-cyanothiazolidine as yellow-brownish crystals.

Workup

  1. customthus obtained
  2. stirringthe mixture was further stirred at room temperature for 1 hour
  3. washThe reaction mixture was washed with an aqueous 10% HCl solution and water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customsubsequently, the residue was crystallized from ether

Sources & evidence

ORD record
ord-63823b7c2ceb4dab96a59eab1d6d937f
Source dataset
uspto-grants-2005_02
Patent number
US06849622B2

Reaction notes

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