Dichloromethane → N-Methoxy-N,2,4-trimethylthiazole-5-carboxamide

HRID 1478501Notes

Reaction equation

HRID 1478501 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.C(Cl)Cl.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:27][NH:28][O:29][CH3:30]>O.[OH-].[Na+].CN(C=O)C>[CH3:30][O:29][N:28]([CH3:27])[C:8]([C:4]1[S:3][C:2]([CH3:1])=[N:6][C:5]=1[CH3:7])=[O:10]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 10559951N-Methoxy-N,2,4-trimethylthiazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a flask containing 2,4-dimethylthiazole-5-carboxylic acid (2.5 g, 15.9 mmol) was added DCM (75 mL) to give a suspension. DMF (3 mL) was added which resulted in a homogeneous solution. Then, carbonyldiimidazole (2.84 g, 17.5 mmol) was introduced and the mixture was stirred at room temperature for 2 hours. N,O-dimethylhydroxylamine HCl (1.9 g, 19.9 mmol) was then added and the mixture was stirred at room temperature for 18 hours, at which time the reaction mixture was diluted with water and 1 N aqueous NaOH and the aqueous portion was extracted with DCM (4×50 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Chromatography on silica gel (10% EtOAc-DCM increasing to 40% EtOAc) provided the title compound as a colorless oil.

Workup

  1. customto give a suspension
  2. customresulted in a homogeneous solution
  3. stirringthe mixture was stirred at room temperature for 18 hours, at which time the reaction mixture
  4. extractionthe aqueous portion was extracted with DCM (4×50 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a0e3225254234905a693657abf1829ad
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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