Cyclohexylamine → HCID 67385155, compound

HRID 2360978Notes

Reaction equation

HRID 2360978 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:27][CH:26]=2)([C:14]([O:16]CC2C=CC=CC=2)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:35]1([NH2:41])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]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]([C:14](=[O:16])[NH:41][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:30]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67384774HCID 67384774, compound

Product 1

HCID 67385155HCID 67385155, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of solution of 4-(4-methoxycarbonyl-benzyl)-piperidine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (9.35 mmol; 3.53 g) in DMF (40 mL) was added cyclohexylamine (11.22 mmol; 1.28 mL), N, N-diisopropyl-N-ethylamine (23.38 mmol; 4.14 mL) and HBTU (11.22 mmol; 4.26 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 70% EtOAc in heptane) to yield 4-cyclohexylcarbamoyl-4-(4-methoxycarbonyl-benzyl)-piperidine-1-carboxylic acid tert-butyl ester after evaporation. The material thus obtained was dissolved in dichloromethane (25 mL) and trifluoroacetic acid (25 mL) was added. The resulting mixture was stirred for 2 hours at room temperature and evaporated. The residue was dissolved in dichloromethane (300 mL) and washed with a saturated sodium bicarbonate solution (50 mL) and brine (50 mL). The organic phase was dried over magnesium sulfate, filtered, and evaporated to yield 4-(4-cyclohexylcarbamoyl-piperidin-4-ylmethyl)-benzoic acid methyl ester. MS (ESI) m/z 459.30 [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 70% EtOAc in heptane)

Sources & evidence

ORD record
ord-c641f7c39a1c4df59139731e0e66a35e
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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