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

HRID 2425483Notes

Reaction equation

HRID 2425483 reaction equation
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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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+)

Workup

  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

Sources & evidence

ORD record
ord-551cbbdb2d7e4506beb40b81374f48f4
Source dataset
uspto-grants-2011_06
Patent number
US07964725B2

Reaction notes

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