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

HRID 1987019Notes

Reaction equation

HRID 1987019 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=O)C.C(Cl)(Cl)Cl>[C:10]([C:6]1[S:5][C:4]([NH:3][C:13](=[O:21])[O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:8][C:7]=1[CH3:9])(=[O:12])[CH3:11]

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 84.8%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

In a round-bottom flask, NaH 60% dispersion in mineral oil (3.07 g, 77 mmol) was washed 2× with hexane and suspended in DMF. Then 2-amino-5-acetyl-4-methyl-thiazole (10.0 g, 64 mmol) was added and stirred while cooling in an ice bath. Stirring continued until the NaH was consumed. Diphenyl carbonate (34 g, 160 mmol) was added while cooling and after the addition was complete the reaction mixture was stirred for an additional 30 minutes at room temperature. The DMF was removed on a rotary evaporator (high vacuum, 40° C.) to yield a brown residue. This residue was dissolved in 1 L of CHCl3 and washed successively with 2 L of 0.5N HCl, 2×1 L of water, and finally by 1 L of brine. The aqueous portions were back extracted twice with 300 ml of CHCl3. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator to give a white solid. This was chromatographed on silica (15%-70% EtOAc/hexane) to give 15 g of the desired carbamate as a white solid. Mp 180-182° C. 1H NMR (300 MHz, CDCl3) δ 11.42 (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). ESI MS: (M+H)+=277.1. Anal. Calcd for C13H12N2O3S: C, 56.51; H, 4.39; N, 10.14; S, 11.60. Found: C, 56.42; H, 4.31; N, 10.11; S, 11.74.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringStirring
  3. customwas consumed
  4. temperaturewhile cooling
  5. additionafter the addition
  6. stirringwas stirred for an additional 30 minutes at room temperature
  7. customThe DMF was removed on a rotary evaporator (high vacuum, 40° C.)
  8. customto yield a brown residue
  9. washwashed successively with 2 L of 0.5N HCl, 2×1 L of water
  10. extractionThe aqueous portions were back extracted twice with 300 ml of CHCl3
  11. dry with materialThe combined organic fractions were dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated on a rotary evaporator
  14. customto give a white solid
  15. customThis was chromatographed on silica (15%-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-9aebedd4378a431087d2470eb8bb62cc
Source dataset
uspto-grants-2009_06
Patent number
US07550486B2

Reaction notes

Loading…