Cyclohexanemethylamine → HCID 67385438, compound

HRID 2360965Notes

Reaction equation

HRID 2360965 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:30]1([CH2:36][NH2:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:22][CH:23]=2)([C:14](=[O:15])[NH:37][CH2:36][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 76688CyclohexanemethylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45074199HCID 45074199, compound

Product 1

HCID 67385438HCID 67385438, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-biphenyl-4-ylmethyl-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (6.32 mmol; 2.5 g) in DMF (50 mL) was added cyclohexylmethylamine (7.59 mmol; 0.99 mL), N,N-diisopropyl-N-ethylamine (15.8 mmol; 2.80 mL) and HBTU (7.59 mmol; 2.88 g), and the resulting mixture was stirred at room temperature overnight. Ethyl acetate (200 mL) was added, and the resulting solution was washed with a 1N hydrochloric acid solution (2×25 mL), and brine (25 mL), and dried over magnesium sulfate. After filtration and evaporation, the residue was purified via flash column chromatography (eluent gradient: 0 to 50% EtOAc in heptane) to yield 4-biphenyl-4-ylmethyl-4-(cyclohexylmethyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester after evaporation. The material thus obtained was dissolved in THF (8 mL) and a 4N HCl solution in 1,4-dioxane (15 mL) was added. The resulting mixture was stirred overnight at room temperature and evaporated. The residue was triturated with diethyl ether and dried to yield 4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide as a hydrochloride salt. MS (ESI) m/z 391.09 [M+H]+.

Workup

  1. washthe resulting solution was washed with a 1N hydrochloric acid solution (2×25 mL), and brine (25 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationAfter filtration and evaporation
  4. customthe residue was purified via flash column chromatography (eluent gradient: 0 to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-979229369c2c4c6e9c3a6ac20c0c8129
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

Loading…