3,5-Bis(trifluoromethyl)benzoic acid → tert-butyl (3R*,4R*)-4-({[3,5-bis(trifluoromethyl)phenyl]carbonyl}amino)-3-(3,4-dichlorophenyl)piperidine-1-carboxylate

HRID 1260907노트

반응식

HRID 1260907 반응식
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C@H:14]1[C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=1.[F:34][C:35]([F:50])([F:49])[C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:39](O)=[O:40].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(#N)C.O.CCN(CC)CC>[F:34][C:35]([F:49])([F:50])[C:36]1[CH:37]=[C:38]([C:39]([NH:12][C@@H:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][C@H:14]2[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)=[O:40])[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=1

참가 물질

8

반응물 4

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86631277HCID 86631277, 화합물

생성물 1

HCID 57741647tert-butyl (3R*,4R*)-4-({[3,5-bis(trifluoromethyl)phenyl]carbonyl}amino)-3-(3,4-dichlorophenyl)piperidine-1-carboxylate수율 98.6%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8471Triethylamine용매

실험 절차

To a solution of the compound (1.48 g) obtained in step 4, 3,5-bis(trifluoromethyl)benzoic acid (1.10 g) and Et3N (0.40 mL) in acetonitrile (15 mL) were added WSC.HCl (1.10 g) and HOBt (0.88 g), 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 saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane) to give the title compound (1.65 g, 98%) as a white powder.

후처리

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-86dc5dc0c0f74da4b8ce398b6697fdc7
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470816B2

반응 노트

불러오는 중…