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

HRID 468650

反応式

HRID 468650 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 66775918Tert-butanol tetrahydrofuran溶媒

実験手順

Cesium carbonate (1.90 g, 5.84 mmol) was added to a solution of the 3,5-difluoro-4-iodopyridin-2(1H)-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, 3H) 1.58 (s, 3H) 2.20 (dt, J=13.90, 7.00 Hz, 1H) 2.52-2.62 (m, 1H) 3.14 (s, 3H) 4.00 (t, J=7.61 Hz, 2H) 4.05-4.22 (m, 2H) 7.94 (dd, J=4.20, 2.05 Hz, 1H).

後処理

  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

出典と根拠

ORDレコード
ord-7d252824ca624984a0d3279a86c7e6d6
出典データセット
uspto-grants-2014_01
特許番号
US08624034B2

関連ノート

読み込み中…