Benzyl Alcohol → tert-Butyl ((trans-4-(((benzyloxy)carbonyl)amino)cyclohexyl)methyl)carbamate

HRID 457685Notes

Reaction equation

HRID 457685 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH:13](C(O)=O)[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:26])C=CC=CC=1.C([N:38]([CH2:41]C)CC)C.[CH2:43]([OH:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1(C)C=CC=CC=1>[CH2:43]([O:50][C:41](=[O:26])[NH:38][CH:13]1[CH2:12][CH2:11][CH:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:15][CH2:14]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 736918(1r,4r)-4-((((Tert-butoxy)carbonyl)amino)methyl)cyclohexane-1-carboxylic acid

Product 1

HCID 22254006tert-Butyl ((trans-4-(((benzyloxy)carbonyl)amino)cyclohexyl)methyl)carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred suspension of 4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexanecarboxylic acid (Maybridge Chemical Co., Ltd.) (45 g) and diphenylphosphoryl azide (44 ml) in toluene (600 ml) was added triethylamine (32 ml) over a period of 20 min whilst maintaining the internal temperature at −10–0 C. The mixture was slowly warmed and then stirred at 70 C for 4 h. After cooling to 40 C, benzyl alcohol (36 ml) was added and the reaction mixture heated at reflux for 20 h. The cold reaction mixture was washed with water and brine and dried over anhydrous magnesium sulfate. Removal of the solvent and recrystallization of the organic residue from ethyl acetate and diethyl ether gave the title compound, benzyl-4-[[[tert-butoxycarbonyl]amino]methyl]cyclohexylcarbamate as a white solid, m.p. 129–131 C.

Workup

  1. temperaturewhilst maintaining the internal temperature at −10–0 C
  2. temperatureThe mixture was slowly warmed
  3. additionwas added
  4. temperaturethe reaction mixture heated
  5. temperatureat reflux for 20 h
  6. customThe cold reaction mixture
  7. washwas washed with water and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customRemoval of the solvent and recrystallization of the organic residue from ethyl acetate and diethyl ether

Sources & evidence

ORD record
ord-74f88bb39a9c49bea77a25d4e111d35e
Source dataset
uspto-grants-2007_03
Patent number
US07189720B2

Reaction notes

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