Hydrochloric Acid → 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo(5,1-c)(1,4)benzoxazine-2-carboxylic acid

HRID 1867255Notes

Reaction equation

HRID 1867255 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[CH:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH:12]=[N:13][N:7]3[C:6]=2[CH:20]=1.CC[C:23]([O-:25])=[O:24].Cl.[OH-].[Na+]>CCO>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[CH:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:12]([C:23]([OH:25])=[O:24])=[N:13][N:7]3[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 866247908-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo(5,1-c)(1,4)benzoxazine 2-ethylcarboxylate

Product 1

HCID 684500928-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo(5,1-c)(1,4)benzoxazine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of the racemic ester (1-6) (0.5 g, 1.5 mmol) in EtOH (10 mL) was treated with 12N HCl (10 mL) and heated at reflux for 8 h. The reaction was cooled to room temperature and neutralized with 3N NaOH and the mixture extracted with EtOAc (50 mL). The organic solution was washed with brine, dried over MgSO4, filtered, and concentrated. The residue was dissolved in MeCN (0.5 mL) and purified by reverse phase HPLC (YMC J-sphere H80 20×50 mm; eluted with 5-95% MeCN/water+0.1% TFA) to provide racemic (3-1). 1H NMR (500 MHz, CDCl3) δ 7.33 (m, 6H), 7.02 (m, 1H), 6.85 (m, 1H), 4.33 (m, 2H), 4.22 (m, 1H), 3.64 (m, 1H) ppm.

Workup

  1. temperatureheated
  2. temperatureat reflux for 8 h
  3. extractionthe mixture extracted with EtOAc (50 mL)
  4. washThe organic solution was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in MeCN (0.5 mL)
  9. custompurified by reverse phase HPLC (YMC J-sphere H80 20×50 mm; eluted with 5-95% MeCN/water+0.1% TFA)

Sources & evidence

ORD record
ord-5b8dfc514bf34f3baf2ebb4b803821f3
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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