Toluene → 8-Fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]-benzoxazine-2-carboxamide
Reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].C[Al](C)C.[F:10][C:11]1[CH:12]=[CH:13][C:14]2[O:19][CH2:18][CH:17]3[CH:20](C4C=CC=CC=4)[CH:21]=[N:22][N:16]3[C:15]=2[CH:29]=1.CCC([O-])=[O:33].[C:35]1([CH3:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[F:10][C:11]1[CH:12]=[CH:13][C:14]2[O:19][CH2:18][CH:17]3[CH:41]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:21]([C:20]([N:3]([O:4][CH3:5])[CH3:2])=[O:33])=[N:22][N:16]3[C:15]=2[CH:29]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A suspension of N-methylmethoxyamine hydrochloride (0.048 g, 0.485 mmol) in dichloromethane (6 mL) at 0° C. was treated with a solution of trimethylaluminum (0.48 mL of a 2.0 M soln in PhMe, 0.971 mmol) and stirred for 20 min. A solution of racemic ester (1-6) (0.150 g, 0.441 mmol) in dichloromethane (2 mL) was added. After stirring for 48 h, the reaction was quenched by the addition of satd. aq. NH4Cl and extracted with EtOAc (2×50 mL). The organic solution was dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (SiO2, 25% EtOAc/hexanes) to provide desired amide (1-7) as a racemic mixture. 1HNMR (500 MHz, CDCl3) δ 7.33-7.35 (m, 4H), 7.17 (m, 1H), 7.10 (m, 1H), 6.80-6.77 (m, 1H), 6.54 (m, 1H), 4.98 (d, J=12.2 Hz, 1H), 4.38 (m, 1H), 3.86-3.82 (m, 4H), 3.30 (br s, 1H) 2.04 (s, 3H) ppm.
Workup
- stirringAfter stirring for 48 h
- customthe reaction was quenched by the addition of satd
- extractionaq. NH4Cl and extracted with EtOAc (2×50 mL)
- dry with materialThe organic solution was dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by flash chromatography (SiO2, 25% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-5a9ad0b06a554460bcbbbc36f0527dba
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07632833B2
Reaction notes
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