Sodium Iodide → (+/-)-Methyl(cis)-1-[2,5-bis(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate

HRID 1869744

반응식

HRID 1869744 반응식
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][C@@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[F:21][C:22]([F:36])([F:35])[C:23]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:24]=1[CH2:25]Br.[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[F:21][C:22]([F:35])([F:36])[C:23]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:27][C:24]=1[CH2:25][N:10]1[CH2:11][CH2:12][C@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:14][C@@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:1])[F:20])=[CH:8][CH:7]=1

참가 물질

8

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27731992-(Bromomethyl)-1,4-bis(trifluoromethyl)benzeneHCID 86617995Methyl(cis)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate

생성물 1

HCID 86617996(+/-)-Methyl(cis)-1-[2,5-bis(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate수율 62%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
150 °C

실험 절차

(±)-Methyl(cis)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate (Example (18b) (88 mg), 2,5-bis(trifluoromethyl)benzyl bromide (110 mg), NaI (25 mg) and K2CO3 (100 mg) in DMF (3 ml) were placed in a microwave tube and the contents were heated in the microwave oven for 20 min at 150° C. The cooled mixture was dispersed between water and EtOAc and the organic extracts were washed with sodium thiosulfate, brine, dried (MgSO4) and evaporated. The crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane to yield a colourless oil (98 mg, 62%) which crystallized on standing. 1H NMR (400 MHz, CDCl3) δ: 1.81-1.89 (2H, m), 1.97 (1H, d, J 13.2), 2.09-2.17 (2H, m), 2.49-2.56 (1H, m), 2.94-2.96 (1H, m), 3.34 (1H, d, J 15.6), 3.40 (1H, dd, J 2.6, 11.3), 3.66 (4H, d, J 15.6), 7.53-7.59 (5H, m), 7.68 (1H, d, J 8.2), 8.19 (1H, s); M/Z (ES+) 514 (MH+).

후처리

  1. washthe organic extracts were washed with sodium thiosulfate, brine
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customThe crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane

출처 및 근거

ORD 기록
ord-864491509d5a4c3287fbef81997926f5
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07638629B2

연결된 노트

불러오는 중…