Pentane → Ethyl 2-((tert-butoxycarbonyl)amino)-1,3-thiazole-4-carboxylate

HRID 85128

Reaction equation

HRID 85128 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[C:12](=O)([O:18]C(C)(C)C)[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].CCCCC>C1COCC1.CN(C)C1C=CN=CC=1>[C:14]([O:13][C:12]([NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1)=[O:18])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 8003PentaneHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 22280595Ethyl 2-((tert-butoxycarbonyl)amino)-1,3-thiazole-4-carboxylateYield 66.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-aminothiazole-4-carboxylate (55; 10.0 g, 58.1 mmol) was taken up in 150 mL of anhydrous THF along with di-tert-butyl carbonate (BOC2O, 12.67 g, 58.1 mmol) along with 10 mg of 4-(dimethyl)aminopyridine (DMAP). The reaction mixture was stirred at 50° C. for 4 h and then at room temperature for 18 h. It was then concentrated under reduced pressure to obtain a thick oil. Pentane was added and the resulting crystalline materials were collected by filtration and dried to afford 10.5 g of ethyl 2-(tert-butoxycarbonylamino)thiazole-4-carboxylate 56. This material 56 (10.5 g, 38.5 mmol) was dissolved in 300 mL of anhydrous THF and cooled in Dry Ice-acetonitrile bath. A solution of 1 M Super Hydride™ in THF (85 mL) was then added over a period of 10 min. The resulting reaction mixture was stirred at −45° C. for 2 h. Another portion of 1 M Super Hydride™ in THF (35 mL) was then added and the reaction mixture was stirred for an additional 2 h at −45° C. The reaction was quenched at −45° C. by the addition of 50 mL of brine. Upon warming to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography to afford 6.39 g of tert-butyl 4-(hydroxymethyl)thiazol-2-ylcarbamate 57 (72%).

Workup

  1. waitat room temperature for 18 h
  2. concentrationIt was then concentrated under reduced pressure
  3. customto obtain a thick oil
  4. filtrationthe resulting crystalline materials were collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-2367d0571e434f118d650bdc11468d31
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Linked notes

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