Hydrogen chloride-ethyl acetate → 9-(3,3-Difluoropyrrolidin-1-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine
Reaction equation
[F:1][C:2]1([F:25])[CH2:6][CH2:5][N:4]([C:7]2[C:17]3[O:16][CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)[CH2:3]1.C(OCC)(=O)C.Cl>C(OCC)(=O)C>[F:25][C:2]1([F:1])[CH2:6][CH2:5][N:4]([C:7]2[C:17]3[O:16][CH2:15][CH2:14][NH:13][CH2:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)[CH2:3]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of tert-butyl 9-(3,3-difluoropyrrolidin-1-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (110 mg, 0.310 mmol), ethyl acetate (2 ml) and 4N hydrogen chloride-ethyl acetate solution (2 ml) was stirred at room temperature for 1 hr, and the solvent was evaporated under reduced pressure. The residue was added to 1N aqueous sodium hydroxide solution (2 ml), and the mixture was extracted with ethyl acetate:tetrahydrofuran (1:1). The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired product (41.0 mg, 52.0%) as a solid.
Workup
- customthe solvent was evaporated under reduced pressure
- additionThe residue was added to 1N aqueous sodium hydroxide solution (2 ml)
- extractionthe mixture was extracted with ethyl acetate:tetrahydrofuran (1:1)
- dry with materialThe extract was dried over anhydrous magnesium sulfate
- customthe solvent was evaporated under reduced pressure
- customThe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:1)
Sources & evidence
- ORD record
- ord-397d2cd3ff9e47fcbf701ac8ff11ea63
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08247403B2
Reaction notes
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