반응 #3140

반응 방정식

acetic acid

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

formaldehyde

sodium cyanoborohydride

→

title compound

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

용매

methanol

methanol

dichloromethane

water

sodium bicarbonate

반응 조건

후처리

1. 1
   온도to warm to room temperature overnight
2. 2
   기타The phases were separated
3. 3
   추출the aqueous layer was extracted with dichloromethane (10 mL)
4. 4
   세척The combined organic phases were washed (brine)
5. 5
   기타dried
6. 6
   기타evaporated
7. 7
   기타to give material which
8. 8
   기타was purified by chromatography with dichloro-methane:methanol (30:1) as the eluent

실험 절차

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.

출처