benzyl N-(2-hydroxycyclohexyl)carbamate → Benzyl (2-oxocyclohexyl)carbamate

HRID 1874249Notes

Reaction equation

HRID 1874249 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>OS(O)(=O)=O.O.CC(C)=O>[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 2

HCID 14785668benzyl N-(2-hydroxycyclohexyl)carbamateHCID 131709961Jones' reagent

Product 1

HCID 14219048Benzyl (2-oxocyclohexyl)carbamateYield 79%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

A mixture of CrO3 (0.70 g) in concentrated H2SO4 (0.61 mL) was diluted with H2O to the volume of 6 mL. To a solution of benzyl 2-hydroxycyclohexylcarbamate (1.60 g, 6.43 mmol) in acetone (5.4 mL) at 0° C. was added Jones Reagent (5.51 mL, 1.17 M, 6.43 mmol) dropwise over 5 min. The reaction mixture was stirred at room temperature for 1.5 h, quenched with 20% aq. K2CO3 to pH=8. The aqueous layer was extracted with EtOAc (3×15 mL). The combined organic layers were washed with sat. NaCl (20 mL), dried over Na2SO4, filtered and concentrated. The resulted crude yellow oil was purified by ISCO chromatography (40 g column) using hexanes/EtOAc (0-30% over 8 min, 30-45% over 10 min) to give benzyl 2-oxocyclohexylcarbamate as a colorless oil at a retention time of 8.5-11 min (1.26 g, 79% yield). HPLC: RT=2.69 min, Purity 99% (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.33 ppm, 5H, m; 5.76 ppm, 1H, s; 5.11 ppm, 2H, m; 4.27 ppm, 1H, m; 2.65 ppm, 1H, dd, J=6.60, 2.75 Hz; 2.52 ppm, 1H, m; 2.38 ppm, 1H, m; 2.13 ppm, 1H, m; 1.89 ppm, 1H, m; 1.77 ppm, 1H, m; 1.64 ppm, 1H, m; 1.42 ppm, 1H, m.

Workup

  1. customquenched with 20% aq. K2CO3 to pH=8
  2. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
  3. washThe combined organic layers were washed with sat. NaCl (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulted crude yellow oil
  8. customwas purified by ISCO chromatography (40 g column)
  9. customhexanes/EtOAc (0-30% over 8 min, 30-45% over 10 min)

Sources & evidence

ORD record
ord-c934c8cc435a4457a50eee8a5483722f
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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