Chloromethyl ethyl ketone → tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-ethylthiazol-2-yl)cyclohexylcarbamate

HRID 2225313Notes

Reaction equation

HRID 2225313 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)[CH2:32][CH3:33]>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]([CH2:32][CH3:33])[N:27]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 69219Chloromethyl ethyl ketoneHCID 86596979tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-carbamothioylcyclohexylcarbamate

Product 1

HCID 86596982tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-ethylthiazol-2-yl)cyclohexylcarbamateYield 36.3%

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, see Example 12f, Step 2) in dry benzene (20 ml) under nitrogen was added 1-chloro-butan-2-one (0.42 g, 0.0039 mol) of and the reaction mixture was heated at 75° C. for over night. Benzene was removed under vaccum and the crude product was extracted with ethyl acetate. The organic layer was washed with brine, concentrated, and purified by recrystallization from ether to give 0.2 g (35%) of tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-ethylthiazol-2-yl)cyclohexylcarbamate as a white solid obtained. 1H NMR (400 MHz, CDCl3) δ 1.27 (t, 3H), 1.44 (s, 9H), 1.62 (m, 2H), 1.81 (m, 3 H), 2.22 (m, 2H), 2.78 (q, 2H), 3.50 (bs, 1H), 3.72 (bs, 1H), 4.12 (bs, 1H), 5.04 (s, 2H), 5.40 (bs, 1H), 5.74 (s, 1H), 7.33 (m, 5H); 13H NMR (400 MHz, CDCl3) 13.45, 24.7, 28.0, 28.24, 28.4, 33.3, 42.3, 47.0, 50.4, 61.0, 66.5, 79.0, 111.6, 127.9, 128.0, 128.4, 136.5, 155.2, 155.8, 158.8, 169.8. MS found: (M+H)+=460.

Workup

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

Sources & evidence

ORD record
ord-389c812a531c475eb4c360b38a129bbd
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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