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

HRID 3044

Reaction equation

HRID 3044 reaction equation
[C:1]([NH:4][C:5]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:10][CH2:9][N:8]([CH:11]([CH2:24][C:25]2[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=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].C=O.[C:47](O)(=O)C.C([BH3-])#N.[Na+]>CO.ClCCl.O.C(=O)(O)[O-].[Na+]>[C:1]([NH:4][C:5]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:6][CH2:7][N:8]([CH:11]([CH2:24][C:25]2[CH:26]=[C:27]([C:35]([F:36])([F:37])[F:38])[CH:28]=[C:29]([C:31]([F:33])([F:32])[F:34])[CH:30]=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][NH:15][CH3:47])[CH2:9][CH2:10]1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 570149314-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Product 1

HCID 867523384-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-methyl-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine (0.30 g) in methanol (4 mL) was added aqueous formaldehyde (37% w/w, 0.027 mL). The mixture was cooled to 0° C. and acetic acid (0.038 mL) was added followed by a solution of sodium cyanoborohydride (43 mg) in methanol (1 mL). The reaction mixture was allowed to warm to room temperature overnight and was diluted with dichloromethane (5 mL), water (5 mL), and saturated sodium bicarbonate (mL). The phases were separated and the aqueous layer was extracted with dichloromethane (10 mL). The combined organic phases were washed (brine), dried, and evaporated, to give material which was purified by chromatography with dichloro-methane:methanol (30:1) as the eluent, to give the title compound as a hemihydrate (0.175 g); mp 72°-74° C.; NMR (d6 -DMSO-trifluoroacetic acid): 7.7 (m,5), 7.25 (m, 6), 3.52 (d,1, J=14.4), 3.25 (d,1, J=14.4), 3.0 (m,1), 2.7-2.45 (m,4), 2.50 (s,3), 2.35-1.95 (broad m,4), 1.85 (s,3), 1.95-1.5 (broad m,4); MS: m/z=674(M+1,100%); TLC: Rf=0.55 (10:1 dichloromethane:methanol). Analysis for C33H35Cl2F6N3O.0.50 H2O: Calculated: C, 57.98; H, 5.31; N, 6.15; Found: C, 57.95; H, 5.24; N, 6.52.

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted with dichloromethane (10 mL)
  4. washThe combined organic phases were washed (brine)
  5. customdried
  6. customevaporated
  7. customto give material which
  8. customwas purified by chromatography with dichloro-methane:methanol (30:1) as the eluent

Sources & evidence

ORD record
ord-be2035c7c1d141fb862b1d083535d3de
Source dataset
uspto-grants-1998_03
Patent number
US05731309

Linked notes

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