Acetic Acid → 4-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

HRID 3041

Reaction equation

HRID 3041 reaction equation
[C:1]([NH:4][C:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][CH:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:14][NH2:15])[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[F:30][C:31]([F:45])([F:44])[C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH:35]=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.ClCCl.O.Cl>[C:1]([NH:4][C:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:10][CH2:9][N:8]([CH:11]([CH2:35][C:34]2[CH:37]=[C:38]([C:40]([F:42])([F:43])[F:41])[CH:39]=[C:32]([C:31]([F:30])([F:44])[F:45])[CH:33]=2)[CH2:12][CH:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:14][NH2:15])[CH2:7][CH2:6]1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 1362473,5-Bis(trifluoromethyl)benzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 195921984-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butylamine

Product 1

HCID 570149314-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butylamine (0.30 g) in methanol (3 mL) was added 3,5-bis(trifluoromethyl)benzaldehyde (0.088 mL) and the mixture cooled to 0° C. To this stirred mixture was sequentially added acetic acid (0.046 mL) and a solution of sodium cyanoborohydride (0.50 g) in methanol (1 mL). The mixture was allowed to slowly warm to room temperature overnight and was diluted with dichloromethane (5 mL), water (5 mL), and hydrochloric acid (1N, 5 mL). The layers were separated, and the aqueous layer was extracted three times with dichloromethane (10 mL). The acidic aqueous layer was made basic with aqueous sodium hydroxide (1N, 5 mL) and then extracted with 5:1 dichloromethane:methanol (3×10 mL). The combined organic layers were washed (brine), dried, filtered and evaporated to afford an oil which was purified by chromatography, with dichloromethane:methanol (40:1) as eluent. Evaporation of the appropriate fractions afforded a partial hydrate of the title compound as a white solid (0.154 g); mp 66°-68° C.; NMR: 7.82 (s,3), 7.75 (s,1), 7.50 (m,2), 7.35-5.15 (m,6), 2.75 (m,1), 2.65-2.55 (m,2), 2.32-1.95 (m,6), 1.85 (s,3), 1.95-1.55 (m,6); MS: m/z=660(M+1, 100%); Rf =0.51 (10:1, dichloromethane:methanol). Analysis for C32H33Cl2F6N3O.0.25 H2O: Calculated: C, 57.79; H, 5.08; N, 6.32; Found: C, 57.68; H, 5.07; N, 6.30.

Workup

  1. temperatureto slowly warm to room temperature overnight
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted three times with dichloromethane (10 mL)
  4. extractionextracted with 5:1 dichloromethane
  5. washThe combined organic layers were washed (brine)
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customto afford an oil which
  10. customwas purified by chromatography, with dichloromethane:methanol (40:1) as eluent
  11. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-7e4da2f6c23d4c1a8affe98a75ef0117
Source dataset
uspto-grants-1998_03
Patent number
US05731309

Linked notes

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