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

HRID 2241937노트

반응식

HRID 2241937 반응식
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]

참가 물질

4

반응물 2

HCID 14917Hydrofluoric Acid2회HCID 59205091methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-tripropan-2-ylsilyloxypropan-2-yl]oxy-benzoate

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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+)

후처리

  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

출처 및 근거

ORD 기록
ord-de26217c17734603b5017e1674a75539
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07671060B2

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