Methanol → 1-(4-fluoro-phenyl)-5-hydroxymethyl-4-isopropyl-1H-pyrazole-3-carboxylic acid methyl ester

HRID 268634ノート

反応式

HRID 268634 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:9]([CH:10]([CH3:12])[CH3:11])=[C:8]([C:13](O)=[O:14])[N:7]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[N:6]=1)=[O:4].B.C1COCC1.CO>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:9]([CH:10]([CH3:12])[CH3:11])=[C:8]([CH2:13][OH:14])[N:7]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[N:6]=1)=[O:4]

参加物

5

反応物 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 247549721-(4-fluoro-phenyl)-4-isopropyl-1 H-pyrazole-3,5-dicarboxylic acid 3-methyl ester

生成物 1

HCID 247546741-(4-fluoro-phenyl)-5-hydroxymethyl-4-isopropyl-1H-pyrazole-3-carboxylic acid methyl ester収率 90%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
25 °C

実験手順

(Reference: J. Med. Chem. 1996, 549-555) To a solution of 1-(4-fluoro-phenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester (15.9 g, 51.8 mmol) in THF (300 mL) at 0° C. was slowly added BH3.THF (1.0 M solution in THF, 104 mL, 104 mmol; commercially available from Sigma Aldrich). The reaction was allowed to warm to 25° C. for 30 min and then heated to 65° C. for 3 hr. After cooling to 25° C., MeOH (50 mL) was slowly added. Subsequently, the solvent was removed under reduced pressure and a second portion of MeOH (100 mL) was slowly added and the solution was stirred at 25° C. for an additional 20 min. The MeOH was then evaporated and EtOAc was added and the organic layer was washed with 1N NaOH and brine prior to drying over Na2SO4. The organic layer was concentrated and purified by silica gel chromatography (15-35% EtOAc/Hex) to provide 1-(4-fluoro-phenyl)-5-hydroxymethyl-4-isopropyl-1H-pyrazole-3-carboxylic acid methyl ester (13.6 g, 90%): H-NMR (CDCl3) δ 7.59-7.56 (m, 2 H), 7.15-7.11 (m, 2 H), 4.57 (s, 2 H), 3.89 (s, 3 H), 3.66-3.62 (m, 1 H), 1.36 (d, 6 H).

後処理

  1. customat 0° C.
  2. temperatureheated to 65° C. for 3 hr
  3. temperatureAfter cooling to 25° C.
  4. customSubsequently, the solvent was removed under reduced pressure
  5. additiona second portion of MeOH (100 mL) was slowly added
  6. customThe MeOH was then evaporated
  7. additionEtOAc was added
  8. washthe organic layer was washed with 1N NaOH and brine
  9. dry with materialto drying over Na2SO4
  10. concentrationThe organic layer was concentrated
  11. custompurified by silica gel chromatography (15-35% EtOAc/Hex)

出典と根拠

ORDレコード
ord-a6942598239645e99e42b4b6d1c24e73
出典データセット
uspto-grants-2008_11
特許番号
US07446121B2

反応ノート

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