Hydrogen Peroxide → 8-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

HRID 1867266Notes

Reaction equation

HRID 1867266 reaction equation
[CH2:1]([C:4]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:8]2[CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[N:7]2[N:6]=[C:5]1[C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[CH:2]=[CH2:3].B1C2CCCC1CCC2.[OH-:39].[Na+].OO>C1COCC1.O.[Cl-].[Na+].O>[F:17][C:14]1[CH:15]=[CH:16][C:11]2[O:10][CH2:9][CH:8]3[C:4]([CH2:1][CH2:2][CH2:3][OH:39])([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:5]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])=[N:6][N:7]3[C:12]=2[CH:13]=1

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 866247943-allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

Product 1

HCID 729864628-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

3-Allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-6; a racemic mixture, 3.7 g, 9.35 mmol) was dissolved in anhydrous THF (50 mL) and treated with a 0.5M solution of 9-BBN (37.4 mL, 18.7 mmol) and stirred at 50° C. for 2 h. The reaction was cooled to 0° C. and treated with 3N NaOH (5 mL) and 30% H2O2 in water (5 mL), and stirred an additional hour. Upon completion, the reaction was treated with brine (50 mL), and extracted with EtOAc (3×100 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude residue was subjected to flash column chromatography (ISCO Redisep 120 g SiO2 column, 0-100% EtOAc/hexanes gradient) to provide pure 8-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-7; a racemic mixture): 1H NMR (300 MHz, CDCl3) δ 7.36-7.19 (m, 5H), 7.15 (dd, J=9.6, 2.9 Hz, 1H), 6.78 (dd, J=8.8, 5.1 Hz, 1H), 6.56 (dt, J=8.8, 3.0 Hz, 1H), 4.00 (dd, J=10.5, 3.5 Hz, 1H), 3.91 (s, 3H), 3.76 (m, 2H), 3.56 (dd, J=11.0, 3.3 Hz, 1H), 3.31 (s, 3H), 2.92 (t, J=10.6 Hz, 1H), 2.60 (dt, J=12.1, 4.9 Hz, 1H), 2.42 (dt, J=12.1, 4.9 Hz, 1H), 1.81 (m, 1H), 1.62 (m, 1H); MS (M+H+, C22H24FN3O4) 414.3 found 414.4 required.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. stirringstirred an additional hour
  3. extractionextracted with EtOAc (3×100 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-424d362be30d401aa8754c0d6ef19d40
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

Loading…