Benzyl Alcohol → ethyl (1R,3S)-3-benzyloxycarbonylaminocyclohexanecarboxylate

HRID 74920Notes

Reaction equation

HRID 74920 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][C@H:8](C(O)=O)[CH2:7]1)=[O:5])[CH3:2].C([N:17]([CH2:20]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])=CC=1.[CH2:39]([OH:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1(C)C=CC=CC=1.O.CCOC(C)=O>[CH2:39]([O:46][C:20]([NH:17][C@H:8]1[CH2:9][CH2:10][CH2:11][C@@H:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7]1)=[O:29])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 111381051-Ethyl (1R,3S)-1,3-cyclohexanedicarboxylate

Product 1

HCID 68101877ethyl (1R,3S)-3-benzyloxycarbonylaminocyclohexanecarboxylateYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

(1S,3R)-3-(Ethoxycarbonyl)cyclohexanecarboxylic acid, 18a, (10.0 g, 49.9 mmol) was dissolved in toluene (100 mL) and treated with triethylamine (7.6 mL, 54.9 mmol) and DPPA (12.2 mL, 54.9 mmol). The resulting solution was heated to 110° C. and stirred for 1 hour. After cooling to 70° C., benzyl alcohol (7.7 mL, 74.9 mmol) was added, and the mixture was heated to 85° C. overnight. The resulting solution was cooled to room temperature, poured into EtOAc (150 mL) and water (150 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2×75 mL) and the combined organic extracts were washed with water (100 mL) and brine (100 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by silica gel chromatography (0%-50% EtOAc/hexanes) to provide 18b (15.3 g, containing ˜25% benzyl alcohol), which was used for the next step without further purification.

Workup

  1. temperatureAfter cooling to 70° C.
  2. temperaturethe mixture was heated to 85° C. overnight
  3. temperatureThe resulting solution was cooled to room temperature
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×75 mL)
  6. washthe combined organic extracts were washed with water (100 mL) and brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by silica gel chromatography (0%-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-cc73e6682ff44e7291562f2bb01bb0b5
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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