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

HRID 3044

반응식

HRID 3044 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매2회HCID 962Water용매HCID 6344Dichloromethane용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
0 °C

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.

후처리

  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

출처 및 근거

ORD 기록
ord-be2035c7c1d141fb862b1d083535d3de
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05731309

연결된 노트

불러오는 중…