Water → 3-(((1S)-2-Hydroxy-1-methylethyl)oxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-(4-(methylsulfonyl)phenoxy)benzamide

HRID 644088ノート

反応式

HRID 644088 の反応式
C[Si](I)(C)C.C[O:7][CH2:8][C@H:9]([CH3:37])[O:10][C:11]1[CH:12]=[C:13]([CH:23]=[C:24]([O:26][C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)[CH:25]=1)[C:14]([NH:16][C:17]1[CH:21]=[CH:20][N:19]([CH3:22])[N:18]=1)=[O:15].O>C(#N)C>[OH:7][CH2:8][C@H:9]([CH3:37])[O:10][C:11]1[CH:12]=[C:13]([CH:23]=[C:24]([O:26][C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:34])=[O:35])=[CH:29][CH:28]=2)[CH:25]=1)[C:14]([NH:16][C:17]1[CH:21]=[CH:20][N:19]([CH3:22])[N:18]=1)=[O:15]

参加物

5

反応物 3

HCID 962WaterHCID 85247Trimethylsilyl iodideHCID 116195273-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[4-(methylsulfonyl)phenoxy]benzamide

生成物 1

HCID 115251163-(((1S)-2-Hydroxy-1-methylethyl)oxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-(4-(methylsulfonyl)phenoxy)benzamide収率 84%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

Trimethylsilyl iodide (11.06 ml, 76.25 mmol) was added to a solution of 3-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[4-(methylsulfonyl)phenoxy]benzamide (7.00 g, 15.25 mmol) in dry acetonitrile (100 ml) under argon for 21 h. Water (40 ml) was added to quench the reaction and the acetonitrile was removed in vacuo. The residue was diluted with ethyl acetate (200 ml) and 1M aqueous hydrochloric acid and the organic layer was separated and further washed with 10% w/v aqueous sodium thiosulfate pentahydrate to remove residual iodine. The organic layer was separated, dried (MgSO4), filtered and evaporated and purified by column chromatography (eluting with 3% to 5% methanol: dichloromethane) to give the title compound (5.70 g, 84%) as a white foam. Recrystallisation from hot ethanol (125 mg/ml) afforded the title compound as colourless needles (87% recovery); 1H NMR (300 MHz, CDCl3) δ: 1.33 (d, 3H), 2.10 (t, 1H), 3.08 (s, 3H), 3.78 (m, 2H), 3.82 (s, 3H), 4.57 (m, 1H), 6.80 (m, 2H), 7.15 (m, 3H), 7.25 (m, 2H), 7.93 (d, 2H), 8.43 (s, 1H); m/z 444 (M−H)−.

後処理

  1. customto quench
  2. customthe reaction
  3. customthe acetonitrile was removed in vacuo
  4. additionThe residue was diluted with ethyl acetate (200 ml) and 1M aqueous hydrochloric acid
  5. customthe organic layer was separated
  6. washfurther washed with 10% w/v aqueous sodium thiosulfate pentahydrate
  7. customto remove residual iodine
  8. customThe organic layer was separated
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. custompurified by column chromatography (eluting with 3% to 5% methanol: dichloromethane)

出典と根拠

ORDレコード
ord-3a0d4edf0ce344bda554651edc81da90
出典データセット
uspto-grants-2010_04
特許番号
US07700640B2

反応ノート

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