Hydrofluoric Acid → methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate

HRID 2241937ノート

反応式

HRID 2241937 の反応式
F.[CH3:2][N:3]([CH3:38])[C:4]([C:6]1[N:7]=[CH:8][C:9]([O:12][C:13]2[CH:14]=[C:15]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:37])[CH2:25][O:26][Si](C(C)C)(C(C)C)C(C)C)[CH:22]=2)[C:16]([O:18][CH3:19])=[O:17])=[N:10][CH:11]=1)=[O:5]>C1COCC1>[CH3:38][N:3]([CH3:2])[C:4]([C:6]1[N:7]=[CH:8][C:9]([O:12][C:13]2[CH:14]=[C:15]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:37])[CH2:25][OH:26])[CH:22]=2)[C:16]([O:18][CH3:19])=[O:17])=[N:10][CH:11]=1)=[O:5]

参加物

4

反応物 2

HCID 14917Hydrofluoric Acid2 回HCID 59205091methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-tripropan-2-ylsilyloxypropan-2-yl]oxy-benzoate

生成物 1

HCID 59205095methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate収率 98%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of hydrogen fluoride (70% in pyridine, 3.25 mL) was added to methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-tripropan-2-ylsilyloxypropan-2-yl]oxy-benzoate in THF (300 mL) in a PTFE vessel and the resulting solution stirred for 18 hours at room temp. Further hydrogen fluoride solution (70% in pyridine, 3.25 mL) was added and the reaction stirred for an additional 66 hours. The reaction was quenched by the very careful addition of saturated aqueous sodium bicarbonate solution until the solution reached pH 8. The aqueous layer was extracted with ethyl acetate (2×500 mL) and the combined organics dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica eluting with 25 to 100% ethyl acetate in isohexane to afford the product (13.2 g, 98%). 1H NMR δ (CDCl3) 1.32 (3H, d), 1.93 (1H, d), 3.17 (6H, d), 3.74-3.79 (1H, m), 3.91 (3H, s), 4.54-4.60 (1H, m), 6.96 (1H, t), 7.43 (1H, d), 7.51 (1H, d), 8.36 (1H, d), 8.53 (1H, d); m/z 376 (M+H+)

後処理

  1. stirringthe reaction stirred for an additional 66 hours
  2. customThe reaction was quenched by the very careful addition of saturated aqueous sodium bicarbonate solution until the solution
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×500 mL)
  4. dry with materialthe combined organics dried (MgSO4)
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by flash column chromatography on silica eluting with 25 to 100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-de26217c17734603b5017e1674a75539
出典データセット
uspto-grants-2010_03
特許番号
US07671060B2

反応ノート

読み込み中…