Triethylamine → tert-butyl 4-{[(3R,4R)-4-{[(4-chlorophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidin-1-yl]methyl}piperidine-1-carboxylate

HRID 1260969노트

반응식

HRID 1260969 반응식
Cl.[Cl:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([N:9]([C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH3:10])=[O:8])=[CH:5][CH:4]=1.[CH:27]([CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O.C(OCC)(=O)C>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]([CH3:10])[C@@H:11]2[CH2:16][CH2:15][N:14]([CH2:27][CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36])[CH2:31][CH2:30]3)[CH2:13][C@H:12]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)=[O:8])=[CH:25][CH:26]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 689287034-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide Monohydrochloride

생성물 1

HCID 68932507tert-butyl 4-{[(3R,4R)-4-{[(4-chlorophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidin-1-yl]methyl}piperidine-1-carboxylate수율 58.9%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

To a mixture of 4-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide monohydrochloride (300 mg) obtained in Example 137a, tert-butyl 4-formylpiperidine-1-carboxylate (735 mg) and triethylamine (105 μL) in acetic acid (0.69 mL)-ethyl acetate (10 mL) was added sodium triacetoxyborohydride (731 mg), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with water and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 60→90% ethyl acetate/hexane, and then 0→30% methanol/ethyl acetate) to give the title compound (242 mg, 58%) as a white powder.

후처리

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with water
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient

출처 및 근거

ORD 기록
ord-b51869cea2f04d91a71776afa2102b87
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470816B2

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