Pyridine → (3S)-tert-butyl 3-((3-hydroxy-5-methyl-3-phenylhex-5-enyl)(methoxycarbonyl)amino)piperidine-1-carboxylate

HRID 884353Notes

Reaction equation

HRID 884353 reaction equation
[OH:1][C:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH2:19][C:20]([CH3:22])=[CH2:21])[CH2:3][CH2:4][NH:5][C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1.C(N(CC)CC)C.N1C=CC=CC=1.Cl[C:43]([O:45][CH3:46])=[O:44]>ClCCl.CCOCC>[OH:1][C:2]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([CH2:19][C:20]([CH3:22])=[CH2:21])[CH2:3][CH2:4][N:5]([C:43]([O:45][CH3:46])=[O:44])[C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:7]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 58278669(3S)-tert-butyl 3-(3-hydroxy-5-methyl-3-phenylhex-5-enylamino)piperidine-1-carboxylate

Product 1

HCID 58278670(3S)-tert-butyl 3-((3-hydroxy-5-methyl-3-phenylhex-5-enyl)(methoxycarbonyl)amino)piperidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3S)-tert-butyl 3-(3-hydroxy-5-methyl-3-phenylhex-5-enylamino)piperidine-1-carboxylate (8.41 g, 21.65 mmol), triethylamine (4.53 mL, 1.5 equiv), pyridine (1.75 mL, 1 equiv) in dichloromethane (250 mL) was cooled to 0° C. Methyl chloroformate (3.35 mL, 2 equiv) was added slowly during a 10 min period. After 15 min, the mixture was warmed to it slowly and stirred 3 h. The mixture was diluted with ether (350 mL), washed with 5% aq HCl solution (2×30 mL), satd aq NaHCO3 solution (25 mL), brine (25 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120 g silica gel column, eluted with a 30-85% EtOAc in hexanes gradient, to afford (3S)-tert-butyl 3-((3-hydroxy-5-methyl-3-phenylhex-5-enyl)(methoxycarbonyl)amino)piperidine-1-carboxylate (5.80 g, 60%). LC-MS Method 1 tR=2.08 min., m/z 447 (M+1).

Workup

  1. temperaturethe mixture was warmed to it slowly
  2. washwashed with 5% aq HCl solution (2×30 mL), satd aq NaHCO3 solution (25 mL), brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by chromatography on a 120 g silica gel column
  6. washeluted with a 30-85% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-dde5563158c44ab2aa30cbedaba84833
Source dataset
uspto-grants-2012_08
Patent number
US08242111B2

Reaction notes

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