Acetonitrile → N-4-Thiazolyl-L-alanine

HRID 327345Notes

Reaction equation

HRID 327345 reaction equation
ClC[C:3]([CH2:5]Cl)=O.[C:7]([O-:10])([O-])=[O:8].[Ca+2].[CH:12]([NH2:14])=[S:13].[CH3:15][C:16]#[N:17]>>[S:13]1[CH:15]=[C:16]([NH:17][C@H:5]([C:7]([OH:10])=[O:8])[CH3:3])[N:14]=[CH:12]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 10112Calcium CarbonateHCID 107931,3-DichloroacetoneHCID 3005587Methanethioamide

Product 1

HCID 53261258N-4-Thiazolyl-L-alanineYield 71%

Procedure

To a solution of the above compound [36a] (40.3 g, 144.1 mmol) in MeCN (160 ml) are added CaCO3 (28 g, 280 mmol, 1.9 eq) and thioformamide (HCSNH2, 14 g, 229.1 mmol, 1.6 eq) and the mixture is stirred at room temperature for 18 hours under nitrogen atmosphere. Insoluble materials are filtered off and the filtrate is concentrated to dryness in vacuo. The residue is dissolved in dichloromethane, subsequently washed with 7% aqueous sodium bicarbonate, 1N NaOH, and water, two times each, to remove non-reacted thioformamide. The dichloromethane layer is dried over MgSO4, concentrated to dryness in vacuo, and subjected to silica gel chromatography (SiO2 : 370 g, MeCN:CH2Cl2 =1:7) to obtain (4-thiazolyl)alanine derivative [37a] (29.15 g, 71%) as an oil.

Workup

  1. filtrationInsoluble materials are filtered off
  2. concentrationthe filtrate is concentrated to dryness in vacuo
  3. dissolutionThe residue is dissolved in dichloromethane
  4. washsubsequently washed with 7% aqueous sodium bicarbonate, 1N NaOH, and water, two times each,
  5. customto remove non-reacted thioformamide
  6. dry with materialThe dichloromethane layer is dried over MgSO4
  7. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-adc8a2814ad44b8485ab48e712e61001
Source dataset
uspto-grants-1993_12
Patent number
US05272268

Reaction notes

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