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

HRID 3041

반응식

HRID 3041 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 313Hydrochloric Acid용매HCID 887Methanol용매2회HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7e4da2f6c23d4c1a8affe98a75ef0117
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05731309

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