반응 #3137

ord-7e4da2f6c23d4c1a8affe98a75ef0117

반응 방정식

CC(=O)O
acetic acid
CC(=O)NC1(c2ccccc2)CCN(CCC(CN)c2ccc(Cl)c(Cl)c2)CC1
4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butylamine
O=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
3,5-bis(trifluoromethyl)benzaldehyde
[BH3-]C#N.[Na+]
sodium cyanoborohydride
CC(=O)NC1(c2ccccc2)CCN(C(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC(CN)c2ccc(Cl)c(Cl)c2)CC1
title compound
CC(=O)NC1(c2ccccc2)CCN(C(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC(CN)c2ccc(Cl)c(Cl)c2)CC1
4-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도to slowly warm to room temperature overnight
  2. 2
    기타The layers were separated
  3. 3
    추출the aqueous layer was extracted three times with dichloromethane (10 mL)
  4. 4
    추출extracted with 5:1 dichloromethane
  5. 5
    세척The combined organic layers were washed (brine)
  6. 6
    기타dried
  7. 7
    여과filtered
  8. 8
    기타evaporated
  9. 9
    기타to afford an oil which
  10. 10
    기타was purified by chromatography, with dichloromethane:methanol (40:1) as eluent
  11. 11
    기타Evaporation of the appropriate fractions

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US05731309uspto-grants-1998_03