Chloroacetone → tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-methylthiazol-2-yl)cyclohexylcarbamate

HRID 2225312Notes

Reaction equation

HRID 2225312 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@@H:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][C@H:13]1[C:26](=[S:28])[NH2:27])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:30][C:31](=O)[CH3:32]>C1C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@@H:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][C@H:13]1[C:26]1[S:28][CH:30]=[C:31]([CH3:32])[N:27]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6571ChloroacetoneHCID 86596979tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-carbamothioylcyclohexylcarbamate

Product 1

HCID 86596981tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-methylthiazol-2-yl)cyclohexylcarbamateYield 44.9%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-carbamothioylcyclohexylcarbamate (0.5 g, 0.0012 mol) in dry benzene (20 mL) under nitrogen was added chloroacetone (0.34 g, 0.0036 mol) and the reaction mixture was heated at 75° C. over night. Benzene was removed under vacuum and the crude was extracted with ethyl acetate. The organic layer was washed with brine, concentrated and purified by recrystallisation from ether to give 0.24 g (44%) of tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-methylthiazol-2-yl)cyclohexylcarbamate as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 1.65 (m, 3H), 1.78 (m, 2H), 2.19 (m, 2H), 2.42 (s, 3H), 3.49 (m, 1H), 3.70 (m, 1H), 4.05 (m, 1H), 5.04 (s, 2H), 5.29 (bs, 1H), 6.75 (s, 1H), 7.34 (m, 5H); 13H NMR (400 MHz, CDCl3) δ 16.4, 27.4, 27.8, 32.7, 41.9, 46.5, 49.7, 66.0, 78.5, 112.3, 127.3, 127.4, 127.8, 135.9, 151.8, 154.6, 155.2, 169.2. MS found: (M+H)+=446.

Workup

  1. customBenzene was removed under vacuum
  2. extractionthe crude was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. concentrationconcentrated
  5. custompurified by recrystallisation from ether

Sources & evidence

ORD record
ord-73420be40eea454494f453d4937798ba
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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