Isocaproaldehyde → N-Butyl-gamma-hydroxy-alpha-(1-methylethyl)-delta-[(4-methylpentyl)amino]cyclohexanehexanamide hydrochloride

HRID 1941353Notes

Reaction equation

HRID 1941353 reaction equation
[ClH:1].[NH2:2][CH:3]([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[CH:4]([OH:17])[CH2:5][CH:6]([CH:14]([CH3:16])[CH3:15])[C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH3:13])=[O:8].C([O-])(=O)C.[Na+].[CH3:30][CH:31]([CH3:36])[CH2:32][CH2:33][CH:34]=O.C([BH3-])#N.[Na+].Cl.C([O-])(O)=O.[Na+]>CO.O.C(O)(=O)C>[NH4+:2].[OH-:8].[ClH:1].[CH2:10]([NH:9][C:7](=[O:8])[CH:6]([CH:14]([CH3:15])[CH3:16])[CH2:5][CH:4]([OH:17])[CH:3]([NH:2][CH2:34][CH2:33][CH2:32][CH:31]([CH3:36])[CH3:30])[CH2:18][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1)[CH2:11][CH2:12][CH3:13]

Participants

11

Reactant 6

HCID 129IsocaproaldehydeHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 19893258delta-Amino-N-butyl-gamma-hydroxy-alpha-(1-methylethyl)cyclohexanehexanamide hydrochloride

Product 2

HCID 14923Ammonium HydroxideHCID 67684659N-Butyl-gamma-hydroxy-alpha-(1-methylethyl)-delta-[(4-methylpentyl)amino]cyclohexanehexanamide hydrochlorideYield 103.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

[αS-(αR*,γR*,δR*)]δ-Amino-N-butyl-γ-hydroxy-α-(1-methylethyl)cyclohexanehexanamide hydrochloride (II: 152 mg, 0.328 mmol), sodium acetate (27 mg, 0.328 mmol) and 4-methylpentanal (36 mg, 0.36 mmol) were dissolved in MeOH (3.2 mL). Sodium cyanoborohydride (20.6 mg, 0.328 mmol) was added and the reaction cooled to 0° C. Acetic acid (0.57 mL, 10.0 mmol) was added dropwise. After the addition was complete the reaction was allowed to warm to r.t. over 3 h. Additional acetic acid was added (0.3 mL) and the reaction was allowed to continue for 30 min. The reaction was brought to a pH of one by the addition of 1N HCl and continued stirring for one h. Water (10 mL) was added and the reaction was neutralized by the addition of solid NaHCO3. The aqueous phase was extracted with CHCl3 (3×15 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Silica gel chromatography (97.5:2.5:0.2 to 96:4:0.2 CH2Cl2 :MeOH:NH4OH gradient) of the concentrate afforded the free amine (76 mg, 56%) which was converted to the hydrochloride salt by treating a MeOH (5 mL) solution of the amine with 1N HCl (0.185 mL). The solvent was removed in vacuo and the residue dissolved in water (20 mL) and EtOH (2 mL). Filtration and lyophilization afforded the title compound (84 mg, 56%) as a white solid.

Workup

  1. additionAfter the addition
  2. temperatureto warm to r.t. over 3 h
  3. extractionThe aqueous phase was extracted with CHCl3 (3×15 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9187991ae12a4039819b422025e3992c
Source dataset
uspto-grants-1997_12
Patent number
US05703129

Reaction notes

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