Water → 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid

HRID 600533Notes

Reaction equation

HRID 600533 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]4[CH2:29][CH2:28][N:27]([CH3:30])[C:26]4=[O:31])[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-].[Li+].O>C1COCC1.CO>[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]4[CH2:29][CH2:28][N:27]([CH3:30])[C:26]4=[O:31])[CH:23]=3)[C:17]([OH:19])=[O:18])=[N:11][CH:12]=2)=[O:6])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 59761154Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate2×

Product 1

HCID 597611423-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acidYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate (Intermediate 7) (304 mg, 0.71 mmol) was dissolved in THF (6 mL) and methanol (2 mL); 1 N lithium hydroxide solution (0.85 mL) was added followed by water (8 mL), and the resultant solution was stirred for 1 hr at room temperature. The majority of the organic solvent was removed by distillation, the remaining aqueous solution was filtered and acidified with 2N hydrochloric acid and extracted with 1:1 ethyl acetate: DCM (2×40 mL). The combined organic extracts were washed with water (10 mL) and brine (20 mL) and dried (MgSO4) to afford the product (265 mg, 96%). 1H NMR δ (300 MHz, CDCl3) 2.12-2.27 (m, 1H), 2.38 (quintet, 2H), 2.52-2.67 (m, 1H), 2.95 (s, 3H), 3.36-3.57 (m, 2H), 4.27 (t, 2H), 4.68 (t, 2H), 4.97 (t, 1H), 7.10 (s, 1H), 7.45 (s, 1H), 7.62 (s, 1H), 8.31 (s, 1H), 8.84 (s, 1H); m/z 413 (M+H)+

Workup

  1. customThe majority of the organic solvent was removed by distillation
  2. filtrationthe remaining aqueous solution was filtered
  3. extractionextracted with 1:1 ethyl acetate
  4. washThe combined organic extracts were washed with water (10 mL) and brine (20 mL)
  5. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-349c9824978544c3a5e1419404f8356a
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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