Acetic Acid → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid

HRID 418013Notes

Reaction equation

HRID 418013 reaction equation
[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:21]=[C:22]([O:24][C@@H:25]([CH3:29])[CH2:26][O:27][CH3:28])[CH:23]=3)[C:17]([O:19]C)=[O:18])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].C(O)(=O)C.Cl>O.CN1CCCC1=O>[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:21]=[C:22]([O:24][C@@H:25]([CH3:29])[CH2:26][O:27][CH3:28])[CH:23]=3)[C:17]([OH:19])=[O:18])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide3×HCID 49765464methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoate

Product 1

HCID 591271113-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
10 °C

Procedure

To a flask was added methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoate (1.0 eq) and N-methylpyrrolidinone (7.6 vols). The contents of the flask were cooled to 10° C. Water (3.9 vols) was added, and the mixture then cooled to approximately −15° C. Sodium hydroxide (1.5 eq) was dissolved in water (2.3 vols), and the sodium hydroxide solution added slowly to the flask over one hour, maintaining the reaction temperature below −10° C. The sodium hydroxide was line washed with water (0.5 vols). The reaction mixture was held for approximately 4 hours. Acetic acid (1.25 eq) was added to the mixture at −10° C. The mixture was allowed to warm to 5° C. Acetic acid (2.37 eq) was added to the mixture, the acetic acid line washed with water (3.5 vols) and the mixture allowed to warm to 22° C. The mixture was seeded, then water (5 vols) was added to the mixture. 2N hydrochloric acid (1.5 eq) was added to the mixture until pH4 was reached. The reaction mixture was stirred for at least 14 hours, then cooled to 10° C., stirred for 1 hour at 10° C. The mixture was filtered. The solid was slurry washed with water (3×2.5 vol). The isolated solid was dried at 25° C. under vacuum to afford the title compound as an off white solid.

Workup

  1. temperaturethe mixture then cooled to approximately −15° C
  2. temperaturemaintaining the reaction temperature below −10° C
  3. washwashed with water (0.5 vols)
  4. temperatureto warm to 5° C
  5. washthe acetic acid line washed with water (3.5 vols)
  6. temperatureto warm to 22° C
  7. additionwater (5 vols) was added to the mixture
  8. temperaturecooled to 10° C.
  9. stirringstirred for 1 hour at 10° C
  10. filtrationThe mixture was filtered
  11. washThe solid was slurry washed with water (3×2.5 vol)
  12. customThe isolated solid was dried at 25° C. under vacuum

Sources & evidence

ORD record
ord-92c9c35d8c99491fafee302729417c0f
Source dataset
uspto-grants-2012_01
Patent number
US08093252B2

Reaction notes

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