Sodium hydride → Tert-butyl 4-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylate

HRID 1666488노트

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HRID 1666488 반응식
[H-].[Na+].[F:3][CH:4](P(=O)(OCC)OCC)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=2)[CH:6]=1.O=[C:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1>CCCCC.C1COCC1>[F:3][C:4]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][N:13]=2)[CH:6]=1)=[C:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86623918Diethyl fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylphosphonate

생성물 1

HCID 66876018Tert-butyl 4-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

NaH (166 mg, 6.92 mmol) under a N2 atmosphere was washed with n-pentane and dried blowing N2 gas. THF (5 mL) was added and the mixture was cooled to 0° C. Diethyl fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylphosphonate (940 mg, 2.3 mmol) was added as a solution in THF dropwise and the mixture was stirred for 30 min. tert-Butyl 4-oxopiperidine-1-carboxylate as a solution in THF was added dropwise and the reaction was stirred for 1 h. Excess NaH was quenched with water at 0° C. and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated to dryness. The residue was purified by column chromatography to give the pure title compound (600 mg). 1H NMR (500 MHz, CDCl3): δ 1.4 (s, 9H), 2.0 (m, 2H), 2.4 (m, 2H), 3.4 (m, 2H), 3.5 (m, 2H), 7.0 (d, 1H, J=8.5 Hz), 7.1-7.2 (m, 4H), 7.4 (t, 1H, J=8 Hz), 7.9 (d, 1H, J=8.5 Hz), 8.4 (s, 1H).

후처리

  1. customdried
  2. additionTHF (5 mL) was added
  3. additionwas added dropwise
  4. customExcess NaH was quenched with water at 0° C.
  5. extractionthe mixture was extracted with ethyl acetate
  6. customThe organic layer was dried
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-a1131f174bc246ac8c83471bc073a87f
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044052B2

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