Hydrogen Peroxide → HCID 76694874, compound

HRID 1867257Notes

Reaction equation

HRID 1867257 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]([Cl: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: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

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 76694873HCID 76694873, compound

Product 1

HCID 76694874HCID 76694874, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

3-Allyl-8-chloro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-2; a racemic mixture, 0.26 g, 0.64 mmol) was dissolved in anhydrous THF (5 mL) and treated with a 0.5M solution of 9-BBN (5.1 mL, 2.6 mmol) and stirred at 50° C. for 2 h. The reaction was cooled to 0° C. and treated with 3N NaOH (1 mL) and 30% H2O2 in water (1 mL), and stirred an additional hour. Upon completion, the reaction was quenched with the addition of brine (5 mL), and extracted with EtOAc (3×10 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude residue was subjected to flash column chromatography (ISCO Redisep 40 g SiO2 column, 0-100% EtOAc/hexanes gradient) to provide pure 8-chloro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-3; a racemic mixture): 1H NMR (300 MHz, CDCl3) δ 7.42 (d, J=2.1 Hz 1H), 7.43-7.24 (m, 5H), 6.83 (d, J=8.5, 2.1 Hz, H), 6.77 (d, J=12.5 Hz, 1H), 3.99 (dd, J=10.5, 3.5 Hz, 1H), 3.91 (s, 3H), 3.76 (br s, 1H), 3.56 (dd, J=11.0, 3.7 Hz, 1H), 3.32 (s, 3H), 2.93 (t, J=10.7 Hz, 1H), 2.59 (dt, J=12.2, 4.9 Hz, 1H), 2.42 (dt, J=12.2, 4.6 Hz, 1H), 1.90-1.60 (m, 4H); MS (M+H+, C22H24ClN3O4) 430.4 found 430.9 required.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. stirringstirred an additional hour
  3. customUpon completion, the reaction was quenched with the addition of brine (5 mL)
  4. extractionextracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4f103c63d21a4927b7b34c23ed6279da
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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