Methanol → 3-[(2S)-1-(Difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoic acid

HRID 2241935Notes

Reaction equation

HRID 2241935 reaction equation
[F:1][CH:2]([F:30])[O:3][CH2:4][C@@H:5]([O:7][C:8]1[CH:9]=[C:10]([CH:15]=[C:16]([O:18][C:19]2[CH:24]=[N:23][C:22]([C:25](=[O:29])[N:26]([CH3:28])[CH3:27])=[CH:21][N:20]=2)[CH:17]=1)[C:11]([O:13]C)=[O:12])[CH3:6].CO.[Li+].[OH-].O>C1COCC1>[F:30][CH:2]([F:1])[O:3][CH2:4][C@@H:5]([O:7][C:8]1[CH:9]=[C:10]([CH:15]=[C:16]([O:18][C:19]2[CH:24]=[N:23][C:22]([C:25](=[O:29])[N:26]([CH3:27])[CH3:28])=[CH:21][N:20]=2)[CH:17]=1)[C:11]([OH:13])=[O:12])[CH3:6]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 59205092Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate

Product 1

HCID 592050903-[(2S)-1-(Difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoic acidYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate (19.8 g, 46.6 mmol) was dissolved in THF (300 mL) and methanol (100 mL) and LiOH (1N, 51.3 mL) was added followed by water dropwise till it went cloudy. The resultant solution was stirred for 16 hours at room temperature. The organics were removed by evaporation under reduced pressure. The aqueous slurry was diluted with water (100 mL), washed with ethyl acetate (200 mL), then acidified by addition of hydrochloric acid (2N) until a solid precipitated. The resulting suspension was extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with water (200 mL) and brine (200 mL), dried (MgSO4), filtered and concentrated under reduced pressure to afford the product (17.2 g, 90%). 1H NMR δ (CDCl3): 1.39 (d, 3H), 3.17 (s, 3H), 3.19 (s, 3H), 3.93-4.05 (m, 2H), 4.60-4.69 (m, 1H), 6.26 (t, 1H), 6.99 (t, 1H), 7.50-7.55 (m, 2H), 8.38 (d, 1H), 8.55 (d, 1H), 10.17 (s, 1H); m/z 412 (M+H)+

Workup

  1. customThe organics were removed by evaporation under reduced pressure
  2. additionThe aqueous slurry was diluted with water (100 mL)
  3. washwashed with ethyl acetate (200 mL)
  4. additionacidified by addition of hydrochloric acid (2N) until a solid
  5. customprecipitated
  6. extractionThe resulting suspension was extracted with ethyl acetate (2×200 mL)
  7. washThe combined organic extracts were washed with water (200 mL) and brine (200 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-51d3422130d04116bcc92b8704629dbb
Source dataset
uspto-grants-2010_03
Patent number
US07671060B2

Reaction notes

Loading…