Cesium carbonate → Tert-butyl 4-(2-(trifluoromethyl)phenoxy)piperidine-1-carboxylate

HRID 1093551

반응식

HRID 1093551 반응식
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].C(=O)([O-])[O-].[Cs+].[Cs+].[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28](OS(C)(=O)=O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C.O>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:2]([F:10])([F:11])[F:1])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 679582-TrifluoromethylphenolHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

생성물 1

HCID 46941590Tert-butyl 4-(2-(trifluoromethyl)phenoxy)piperidine-1-carboxylate수율 34%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

To a stirred solution of 2-trifluoromethyl-phenol (1 g, 0.00617 mole) in DMF (10 mL) was added cesium carbonate (4.01 g, 0.0123 mole), followed by 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (1.72 g, 0.00616 mole). The reaction mixture was heated at 60° C. overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (0.1% ethyl acetate in hexane) to afford 0.72 g (34%) of 4-(2-trifluoromethyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS: 346.16 (M+1)+, 94.42%. A solution of 4-(2-trifluoromethyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (0.72 g, 0.00208 mole) in dichloromethane was stirred at 0-5° C. To the cold solution was added TFA (1 mL) dropwise and stirring was continued at 10° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was washed with ether and dried to afford 0.22 g (99%) of 4-(2-trifluoromethyl-phenoxy)-piperidine trifluoracetate. LCMS: 360.1 (M+1)+, 99.3%, 1H NMR (CDCl3): δ 8.9-8.5 (bd, 2H), 7.62-7.6 (d, 1H), 7.56-7.46 (t, 1H), 7.1-7.02 (t, 1H), 7.0-6.94 (d, 1H), 5.0-4.8 (m, 1H), 3.5-3.3 (s, 4H), 2.3-2.2 (s, 4H).

후처리

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-530db52ba4594a4da6723c8fc503f65e
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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