2-(Tert-butyldimethylsilyloxymethyl)-4-bromothiazole → 1-[2-(tert-butyldimethylsilanyloxymethyl)thiazol-4-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

HRID 244481ノート

反応式

HRID 244481 の反応式
Br[C:2]1[N:3]=[C:4]([CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[S:5][CH:6]=1.[Li]CCCC.[F:21][C:22]([F:42])([F:41])[C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[N:29]=[CH:28]2)=[O:24]>CCOCC>[Si:9]([O:8][CH2:7][C:4]1[S:5][CH:6]=[C:2]([C:23]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[N:29]=[CH:28]3)([OH:24])[C:22]([F:41])([F:21])[F:42])[N:3]=1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]

参加物

5

反応物 3

HCID 167365792-(Tert-butyldimethylsilyloxymethyl)-4-bromothiazoleHCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 178418339Butyllithium

生成物 1

HCID 594372131-[2-(tert-butyldimethylsilanyloxymethyl)thiazol-4-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol収率 67%

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒2 回

実験手順

To a chilled (−78° C.) solution of 4-bromo-2-(tert-butyldimethylsilanyloxymethyl)thiazole (339 mg, 1.10 mmol) (prepared according to a procedure described by Nicolaou et al., Bioorg. Med. Chem. 1999, 7, 665-697) in dry ether (5 mL) was added n-BuLi (440 μL, 2.5 M in hexane, 1.10 mmol). After 2 minutes, a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (308 mg, 1.00 mmol) in 5 mL of dry ether added. After 15 minutes, the mixture was warmed to room temperature and quenched with 20 mL of saturated aqueous ammonium chloride and extracted with three 20 mL portions of diethyl ether. The combined organic layers were washed with 20 mL of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on SiO2 (0-30% ethyl acetate in hexanes, gradient) to afford 358 mg (67%) of 1-[2-(tert-butyldimethylsilanyloxymethyl)thiazol-4-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol. MS m/z 538.97 (MH+).

後処理

  1. customprepared
  2. additionadded
  3. waitAfter 15 minutes
  4. customquenched with 20 mL of saturated aqueous ammonium chloride
  5. extractionextracted with three 20 mL portions of diethyl ether
  6. washThe combined organic layers were washed with 20 mL of brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on SiO2 (0-30% ethyl acetate in hexanes, gradient)

出典と根拠

ORDレコード
ord-80341a175b7241b697327e7f1f167228
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

反応ノート

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