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

HRID 1941353노트

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HRID 1941353 반응식
[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]

참가 물질

11

반응물 6

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

생성물 2

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

시약·촉매·용매 3

HCID 176Acetic Acid용매2회HCID 887Methanol용매HCID 962Water용매

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온도
0 °C

실험 절차

[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.

후처리

  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

출처 및 근거

ORD 기록
ord-9187991ae12a4039819b422025e3992c
출처 데이터셋
uspto-grants-1997_12
특허 번호
US05703129

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