Diphenyl carbonate → Phenyl (5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamate

HRID 896533Notes

Reaction equation

HRID 896533 reaction equation
[H-].[Na+].[NH2:3][C:4]1[S:5][C:6]([C:10](=[O:12])[CH3:11])=[C:7]([CH3:9])[N:8]=1.[C:13](=O)([O:21]C1C=CC=CC=1)[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CCCCCC.CN(C)C=O.C(Cl)(Cl)Cl>[C:15]1([O:14][C:13](=[O:21])[NH:3][C:4]2[S:5][C:6]([C:10](=[O:12])[CH3:11])=[C:7]([CH3:9])[N:8]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 3

HCID 7597Diphenyl carbonateHCID 24758Sodium hydride2×HCID 7208825-Acetyl-2-amino-4-methylthiazole

Product 1

HCID 22259036Phenyl (5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamateYield 85%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 3.07 g, 77 mmol) was washed twice with hexane and suspended in N,N-dimethylformamide. 2-Amino-5-acetyl-4-methylthiazole (10.0 g, 64 mmol) was added with stirring and cooling on an ice bath. Stirring was continued until the sodium hydride was consumed. Diphenyl carbonate (34 g, 160 mmol) was added and the mixture was stirred for 30 minutes at room temperature. The solvent was removed under vacuum to yield a brown residue, which was dissolved in chloroform and washed successively with 0.5N aqueous hydrochloric acid, twice with water and finally with saturated aqueous sodium chloride. The aqueous phases were back extracted twice with chloroform. The combined organic fractions were dried over sodium sulfate and concentrated under vacuum to give a white solid. This was chromatographed on silica gel, eluting with 15%-70% ethyl acetate in hexane, to give a white solid (15.0 g, 85%). 1H NMR (300 MHz, CDCl3) δ11.42 (bs, 1H), 7.47-7.40 (m, 2H), 7.33-7.27 (m, 1H), 7.22-7.18 (m, 2H), 2.72 (s, 3H), 2.50 (s, 3H). Mass spec (ES+) m/z 277.1 (M+H+).

Workup

  1. temperaturecooling on an ice bath
  2. stirringStirring
  3. customwas consumed
  4. stirringthe mixture was stirred for 30 minutes at room temperature
  5. customThe solvent was removed under vacuum
  6. customto yield a brown residue, which
  7. washwashed successively with 0.5N aqueous hydrochloric acid, twice with water and finally with saturated aqueous sodium chloride
  8. extractionThe aqueous phases were back extracted twice with chloroform
  9. dry with materialThe combined organic fractions were dried over sodium sulfate
  10. concentrationconcentrated under vacuum
  11. customto give a white solid
  12. customThis was chromatographed on silica gel
  13. washeluting with 15%-70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-20e8e85a2fbd47e9ba0dc364f345f2a6
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

Loading…