Potassium tert-butoxide → Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoate

HRID 1849916노트

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HRID 1849916 반응식
[CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.O>[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=[CH2:1])[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]

참가 물질

6

반응물 2

HCID 23665647Potassium tert-butoxideHCID 86703687Methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate

생성물 1

HCID 86703796Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoate수율 83.3%

시약·촉매·용매 3

HCID 74505Methyltriphenyliphosphonium bromide촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

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온도
0 °C

실험 절차

To a suspension of methyltriphenylphosphonium bromide (1.61 g, 4.51 mmol) in anhydrous tetrahydrofuran (20 mL) was added a solution of potassium tert-butoxide (0.541 g, 4.82 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes at 0° C. The mixture was stirred under a nitrogen atmosphere at 0° C. for 1 h. To this solution was added a solution of methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate (1.05 g, 3.48 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes. The mixture was stirred at ambient temperature for 21 h, then diluted with water (200 mL). The mixture was extracted with ethyl acetate (200 mL) and the organic phase was washed with water (50 mL) and brine (150 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a colorless syrup (0.866 g, 83% yield): 1H NMR (300 MHz, CDCl3) δ 7.94 (d, J=7.7 Hz, 1H), 6.67 (d, J=12.2 Hz, 1H), 4.68 (s, 2H), 4.56-4.50 (m, 1H), 3.87 (s, 3H), 2.48-2.40 (m, 2H), 2.17-2.09 (m, 2H), 1.92-1.86 (m, 4H); MS (ES+) m/z 299.00 (M+1).

후처리

  1. stirringThe mixture was stirred at ambient temperature for 21 h
  2. extractionThe mixture was extracted with ethyl acetate (200 mL)
  3. washthe organic phase was washed with water (50 mL) and brine (150 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-6ecaa4680b5f47b990b39ed4ace75ac4
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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