Sodium hydride → Tert-butyl 4-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666465노트

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HRID 1666465 반응식
[H-].[Na+].[CH:3]1([C:6]2[CH:7]=[C:8]([CH:18]=[C:19]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][N:23]=3)[CH:20]=2)[CH2:9]P(=O)(OCC)OCC)[CH2:5][CH2:4]1.[C:32]([N:39]1[CH2:44][CH2:43][CH2:42][CH2:41][C:40]1=O)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH:3]1([C:6]2[CH:7]=[C:8]([CH:18]=[C:19]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][N:23]=3)[CH:20]=2)[CH:9]=[C:42]2[CH2:43][CH2:44][N:39]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:40][CH2:41]2)[CH2:4][CH2:5]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 86623909HCID 86623909, 화합물

생성물 1

HCID 66875428Tert-butyl 4-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate수율 46.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
0 °C

실험 절차

To a suspension of sodium hydride (0.11 g, 4.65 mmol) in dry THF (1.5 mL) under an inert atmosphere cooled to 0° C. was added diethyl 3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate (0.8 g, 1.86 mmol) as a solution in THF (6 mL). The mixture was stirred for 30 min at 0° C. N-Boc piperidone (0.37 g, 1.86 mmol) was added as a solution in THF (3 mL) and the mixture was stirred at RT for 5 h. The reaction was cooled to 0° C. and quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography (10% ethyl acetate in hexane) to give the title compound (0.408 g, 46%). 1H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.87 (d, J=8 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 6.68 (s, 1H), 6.30 (s, 1H), 3.49 (m, 2H), 3.39 (m, 2H), 2.45 (m, 2H), 2.31 (m, 2H), 1.88 (m, 1H), 1.46 (s, 9H), 0.96 (d, J=8.5 Hz, 2H), 0.69 (d, J=4.5 Hz, 2H); m/z (475.1, M+ H+).

후처리

  1. stirringthe mixture was stirred at RT for 5 h
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionThe mixture was extracted with ethyl acetate three times
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customThe residue was purified by silica gel column chromatography (10% ethyl acetate in hexane)

출처 및 근거

ORD 기록
ord-60c50977a40340e9b66a1711c95df9b1
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044052B2

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