Water → Ethyl (2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 84294노트

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HRID 84294 반응식
C(=O)([O-])[O-].[K+].[K+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:16][C:17]1[C:18](I)=[CH:19][C:20](=[O:36])[N:21]([CH2:23][CH2:24][C@@:25]([CH3:35])([S:31]([CH3:34])(=[O:33])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:22]=1.O>O1CCOCC1.[Pd]>[F:16][C:17]1[C:18]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:19][C:20](=[O:36])[N:21]([CH2:23][CH2:24][C@@:25]([CH3:35])([S:31]([CH3:34])(=[O:32])=[O:33])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:22]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 67249679Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

생성물 1

HCID 67248183Ethyl (2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate수율 88.3%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

Pd EnCat™ (95 mg, 0.037 mmol) was added to a mixture of potassium carbonate (312 mg, 2.26 mmoll), phenylboronic acid (131 mg, 1.07 mmol), and ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (319 mg, 0.716 mmol) in dioxane:water (10 ml, 4:1) in a 20 mL vial equipped with a stir bar. The reaction was heated to 90° C. and allowed to stir overnight at that temperature. The reaction was allowed to cool to RT, filtered and the catalyst was washed with methanol (10 ml) and dichloromethane (10 ml). The filtrate was concentrated to afford a crude solid. The crude was purified via flash chromatography using an Analogix SF15-12 column and an eluant of ethyl acetate in heptane (50-100%) and methanol in ethyl acetate (0-5%) to afford the title compound as a yellowish white solid (250 mg, 64.8%). LC-MS m/z 396.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (t, J=7.12 Hz, 3 H) 1.62 (s, 3 H) 2.15-2.32 (m, 1 H) 2.53-2.66 (m, 1 H) 3.16 (s, 3 H) 3.89-4.06 (m, 2 H) 4.07-4.26 (m, 2 H) 6.50 (d, J=7.61 Hz, 0 H) 7.20-8.12 (m, 6 H).

후처리

  1. temperatureto cool to RT
  2. filtrationfiltered
  3. washthe catalyst was washed with methanol (10 ml) and dichloromethane (10 ml)
  4. concentrationThe filtrate was concentrated
  5. customto afford a crude solid
  6. customThe crude was purified via flash chromatography

출처 및 근거

ORD 기록
ord-ee8c500c17204174a9d9605a5e85a8c9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846933B2

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