Diisopropylethylamine → Tert-butyl 1-(3-bromo-5-fluoropyridin-4-yl)piperidine-4-carboxylate

HRID 524888노트

반응식

HRID 524888 반응식
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:9])[C:7]=1Cl.[F-].[K+].Cl.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.CCN(C(C)C)C(C)C>[N+](C)(C)(C)C.[Cl-].CS(C)=O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:9])[C:7]=1[N:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 42614227Piperidine-4-carboxylic acid tert-butyl ester hydrochlorideHCID 709772193-Bromo-4-chloro-5-fluoropyridine

생성물 1

HCID 86720943Tert-butyl 1-(3-bromo-5-fluoropyridin-4-yl)piperidine-4-carboxylate수율 65.3%

시약·촉매·용매 2

HCID 6379Tetramethylammonium chloride촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
130 °C

실험 절차

A thoroughly stirred mixture of 3-bromo-4-chloro-5-fluoropyridine free base (55 g, 0.26 mol), potassium fluoride (31 g, 0.53 mol) and Me4NCl (5.8 g, 53 mmol) in DMSO (400 mL) was heated to 130° C. for 2 hours. The reaction mixture was cooled to room temperature and tert-butyl piperidine-4-carboxylate hydrochloride 22 (66 g, 0.30 mol) and DIPEA (65 g, 0.50 mol) were added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo. The residue was portioned between DCM/water. The organic layer was washed with water (3×), dried over Na2SO4, and filtered over silica gel using DCM as eluent. The filtrated was evaporated to give tert-butyl 1-(3-bromo-5-fluoropyridin-4-yl)piperidine-4-carboxylate 26 (61 g, 65%) as a light yellow solid; 1H NMR (500 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.41 (d, 1H), 3.39-3.36 (m, 2H), 3.12 (tt, 2H), 2.49-2.43 (m, 1H), 1.91-1.87 (m, 2H), 1.71-1.64 (m, 2H) and 1.43 (s, 9H); 19F NMR (500 MHz, DMSO-d6) δ −135.2; MS (ES+) 361.0.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe solvent was evaporated in vacuo
  3. washThe organic layer was washed with water (3×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered over silica gel
  6. customThe filtrated was evaporated

출처 및 근거

ORD 기록
ord-3cfe3048887a4e94a4bf1b2edf9d095b
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340546B2

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