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

HRID 2425486Notes

Reaction equation

HRID 2425486 reaction equation
[CH3:1][N:2]([CH3:31])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([O:22][C@@H:23]([CH3:30])[CH2:24][O:25]C(C)(C)C)[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4].C(OCC)(=O)C.O>C(O)=O.[Cl-].[Na+].O>[CH3:31][N:2]([CH3:1])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([O:22][C@@H:23]([CH3:30])[CH2:24][OH:25])[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4]

Participants

6

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 59205102Methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-[(2-methylpropan-2-yl) oxy]propan-2-yl]oxy-benzoate

Product 1

HCID 59205095methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoateYield 101.1%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-[(2-methylpropan-2-yl)oxy]propan-2-yl]oxy-benzoate (170 g, 0.39 mol) in formic acid (850 mL) was heated to 90° C. for 3 hours. Ethyl acetate (1700 mL), water (1700 mL) and saturated aqueous brine (850 mL) was added and the aqueous layer separated and extracted with ethyl acetate (850 mL) and the combined organic layers were washed with saturated aqueous brine (850 mL), dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved with ethyl acetate (1500 mL), water (1500 mL) and methanol (150 mL). Sodium carbonate (170 g) was added and the biphasic solution heated to reflux for 2 hours. The aqueous layer was separated and the organic layer washed with water (1700 mL). The combined aqueous phases were extracted with ethyl acetate (850 mL) and the combined organic layers dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography eluting with 100% ethyl acetate to obtain a the title compound (148 g).

Workup

  1. customthe aqueous layer separated
  2. extractionextracted with ethyl acetate (850 mL)
  3. washthe combined organic layers were washed with saturated aqueous brine (850 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated under reduced pressure
  6. dissolutionThe residue was dissolved with ethyl acetate (1500 mL), water (1500 mL) and methanol (150 mL)
  7. additionSodium carbonate (170 g) was added
  8. temperaturethe biphasic solution heated
  9. temperatureto reflux for 2 hours
  10. customThe aqueous layer was separated
  11. washthe organic layer washed with water (1700 mL)
  12. extractionThe combined aqueous phases were extracted with ethyl acetate (850 mL)
  13. dry with materialthe combined organic layers dried (MgSO4)
  14. customevaporated under reduced pressure
  15. customThe residue was purified by flash chromatography
  16. washeluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-710121bb2c8f41c3be728a406c58bbc5
Source dataset
uspto-grants-2011_06
Patent number
US07964725B2

Reaction notes

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