Dichloromethane → Benzyl 1-cyano-4-fluoro-4-(hydroxymethyl)cyclohexylcarbamate

HRID 75725Notes

Reaction equation

HRID 75725 reaction equation
[NH2:1][C:2]1([C:11]#[N:12])[CH2:7][CH2:6][C:5]([F:10])([CH2:8][OH:9])[CH2:4][CH2:3]1.C(Cl)Cl.[C:16](Cl)(=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O>[C:11]([C:2]1([NH:1][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:3][CH2:4][C:5]([F:10])([CH2:8][OH:9])[CH2:6][CH2:7]1)#[N:12]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 10387Benzyl chloroformateHCID 67958695HCID 67958695, compound

Product 1

HCID 67977046Benzyl 1-cyano-4-fluoro-4-(hydroxymethyl)cyclohexylcarbamateYield 60.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A flask was charged with 1-amino-4-fluoro-4-(hydroxymethyl)cyclohexanecarbonitrile, Intermediate 32, (12.2 g, 70.8 mmol), CH2Cl2 (200 mL), water (80 mL) and benzyl chlorocarbonate (12.14 mL, 85 mmol) and the mixture stirred under nitrogen overnight. The CH2Cl2 portion of the reaction mixture was separated, washed with water then brine, dried (MgSO4) and concentrated to give a yellow oil. The oil was purified by column chromatography on silica gel, eluted with hexane/ethyl acetate (0 to 100%). The appropriate fractions were combined and the solvent evaporated to provide the title compound (13.1 g, 42.8 mmol, 60.4% yield)] as a colorless oil that crystallized upon standing.

Workup

  1. customThe CH2Cl2 portion of the reaction mixture was separated
  2. washwashed with water
  3. dry with materialbrine, dried (MgSO4)
  4. concentrationconcentrated
  5. customto give a yellow oil
  6. customThe oil was purified by column chromatography on silica gel
  7. washeluted with hexane/ethyl acetate (0 to 100%)
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-900dd7d49942478c95ed9f731f762f39
Source dataset
uspto-grants-2014_09
Patent number
US08835411B2

Reaction notes

Loading…