Methyl 3-(2-amino-4-fluorophenylamino)-2-methylpropanoate → 8-fluoro-3-methyl-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one
Reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH:11]([CH3:16])[C:12](OC)=[O:13]>C1(C)C=CC=CC=1.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4]>[F:8][C:6]1[CH:5]=[CH:4][C:3]2[NH:9][CH2:10][CH:11]([CH3:16])[C:12](=[O:13])[NH:1][C:2]=2[CH:7]=1Participants
4
Conditions
- Temperature
- 90 °C
Procedure
To a solution of methyl 3-(2-amino-4-fluorophenylamino)-2-methylpropanoate (10.0 g, 44.2 mmol) in toluene (200 mL) was added titanium tetraisopropanolate (18.8 g, 66.3 mmol). The mixture was stirred at 90° C. for 15 hours. The resultant mixture was concentrated in vacuo, and dissolved in tetrahydrofuran (200 mL), filtered through celite, and washed with tetrahydrofuran (100 mL). The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to afford 8-fluoro-3-methyl-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one as a black solid (6.5 g, 76%).
Workup
- concentrationThe resultant mixture was concentrated in vacuo
- dissolutiondissolved in tetrahydrofuran (200 mL)
- filtrationfiltered through celite
- washwashed with tetrahydrofuran (100 mL)
- concentrationThe filtrate was concentrated in vacuo
- customthe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1)
Sources & evidence
- ORD record
- ord-183c1f57e8fe468f894be87b18a10167
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09422292B2
Reaction notes
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