Chloroacetone → benzyl [(1S,2S)-2-hydroxy-1-methyl-2-(4-methyl-1,3-thiazol-2-yl)ethyl]carbamate

HRID 1028615Notes

Reaction equation

HRID 1028615 reaction equation
[NH2:1][C:2](=[S:25])[C@@H:3]([O:17][Si](C(C)(C)C)(C)C)[C@@H:4]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:5].Cl[CH2:27][C:28](=O)[CH3:29]>CCO>[OH:17][C@H:3]([C:2]1[S:25][CH:27]=[C:28]([CH3:29])[N:1]=1)[C@@H:4]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH3:5]

Participants

4

Reactant 2

HCID 6571ChloroacetoneHCID 86603432benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate

Product 1

HCID 86603433benzyl [(1S,2S)-2-hydroxy-1-methyl-2-(4-methyl-1,3-thiazol-2-yl)ethyl]carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate (96.8 mg, 0.253 mmol) and chloroacetone (117 mg, 101 μL, 1.27 mmol) in dry EtOH (5 mL) was heated at reflux under N2 for 20 h, then stirred at room temperature for 2 days. The reaction mixture was concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-100% EtOAc in hexanes gradient) to afford benzyl [(1S,2S)-2-hydroxy-1-methyl-2-(4-methyl-1,3-thiazol-2-yl)ethyl]carbamate. Rf=0.44 (50% EtOAc in hexanes). LCMS calc.=307.1; found=307.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.31 (m, 5H), 6.80 (s, 1H), 5.49 (br s, 1H), 5.06 (m, 3H), 4.26-4.18 (m, 1H), 2.38 (s, 3H), 1.09 (d, J=6.5 Hz, 3H).

Workup

  1. temperatureat reflux under N2 for 20 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give the crude product
  4. customThis was purified by flash chromatography (Si, 12×160 mm, 0-100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-51ade34f298a43ae97a44adaccde7836
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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