Cesium carbonate → Ethyl (2R)-4-(3,5-difluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 1625046노트

반응식

HRID 1625046 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[C:9](=[O:16])[NH:10][CH:11]=[C:12]([F:15])[C:13]=1[I:14].Br[CH2:18][CH2:19][C@@:20]([CH3:30])([S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22]>O1CCCC1.C(O)(C)(C)C>[F:7][C:8]1[C:9](=[O:16])[N:10]([CH2:18][CH2:19][C@@:20]([CH3:30])([S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:11]=[C:12]([F:15])[C:13]=1[I:14]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 706651963,5-difluoro-4-iodopyridin-2(1H)-oneHCID 86670635(R)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

생성물 1

HCID 86670654Ethyl (2R)-4-(3,5-difluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate수율 32%

시약·촉매·용매 1

HCID 66775918Tert-butanol tetrahydrofuran용매

실험 절차

Cesium carbonate (1.90 g, 5.84 mmol) was added to a solution of the 3,5-difluoro-4-iodopyridin-2(1 H)-one (1.0 g, 3.9 mmol) and ethyl (2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate, T1, (1.45 g, 5.06 mmol) in tetrahydrofuran:t-butanol (1:1, 50 mL). The resulting suspension was heated to reflux and was stirred at this temperature for 72 h. The reaction was filtered through celite, and the filter pad was washed with EtOAc (3×50 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography on an Analogix SF15-24 g column using an eluent of EtOAc in hexanes (0-50%) to afford the title compound as a yellow solid (575.6 mg, 32%). MS (LCMS) m/z 463.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (s, 3 H) 1.58 (s, 3 H) 2.20 (dt, J=13.90, 7.00 Hz, 1 H) 2.52-2.62 (m, 1 H) 3.14 (s, 3 H) 4.00 (t, J=7.61 Hz, 2 H) 4.05-4.22 (m, 2 H) 7.94 (dd, J=4.20, 2.05 Hz, 1 H).

후처리

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux
  3. filtrationThe reaction was filtered through celite
  4. washthe filter pad was washed with EtOAc (3×50 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customthe crude product was purified via flash chromatography on an Analogix SF15-24 g column

출처 및 근거

ORD 기록
ord-40ffdf64f9d84abb92451755839cd466
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779148B2

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