tert-Butanol → [4-(4-Chloro-phenyl)-cyclohexyl]-carbamic acid tert-butyl ester

HRID 1021524Notes

Reaction equation

HRID 1021524 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][CH:11](C(O)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([N:19]([CH2:22]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:25]C1C=CC=CC=1.[C:43]([OH:47])([CH3:46])([CH3:45])[CH3:44]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][CH:11]([NH:19][C:22](=[O:25])[O:47][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 27357924-(4-Chlorophenyl)cyclohexane-1-carboxylic acid

Product 1

HCID 67080532[4-(4-Chloro-phenyl)-cyclohexyl]-carbamic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-chlorophenyl)cyclohexanecarboxylic acid (1.01 g, 4.231 mmol) and triethylamine (0.5897 ml, 4.231 mmol) in tert-butanol (22 ml) was added diphenyl phosphorazidate (0.9147 ml, 4.231 mmol), and the reaction was heated to reflux for 16 hours. The reaction was diluted with EtOAc and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was on a Biotage SP1 system eluting with a linear gradient of 5-50% EtOAc in hexanes to yield 760 mg of the title compound (57% yield).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 16 hours
  3. washwashed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluting with a linear gradient of 5-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-0eeb6d6c71bd44208ff5b774f6db8b62
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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