Ethyl Acetate → 8-Bromo-2-methoxy-1,5-naphthyridine
Reaction equation
F[C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[CH:7][CH:8]=[N:9]2)=[N:4][CH:3]=1.P(Br)(Br)[Br:14].CCO[C:20](C)=[O:21]>CN(C=O)C>[Br:14][C:6]1[CH:7]=[CH:8][N:9]=[C:10]2[C:5]=1[N:4]=[C:3]([O:21][CH3:20])[CH:2]=[CH:11]2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 7-fluoro-1,5-naphthyridin-4-ol (400 mg, 2.43 mmol) in DMF (8 mL), was added PBr3 (659.65 mg, 2.43 mmol) dropwise at 50° C. for 10 minutes. After complete addition of PBr3, the suspension became homogeneous and a brown precipitate was obtained over a period of 30 minutes. The reaction was monitored by TLC (TLC eluent: 50% EtOAc in petroleum ether). After completion of reaction, the mixture was cooled to ambient temperature to generate more precipitate. The precipitate was filtered and washed with Et2O (15 mL) and dried under vacuum to afford a brown colored hydro bromide salt of 8-bromo-2-methoxy-[1,5]naphthyridine which was free-based using saturated bicarbonate solution (10 mL) and product was extracted into EtOAc (2×25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 8-bromo-3-fluoro-1,5-naphthyridine as a brown solid, (200 mg, 36%). 1H NMR (300 MHz, DMSO-d6): δ 9.19 (d, J=2.4 Hz, 1H), 8.84 (d, J=4.8 Hz, 1H), 8.44 (dd, J=2.8 & 9.2 Hz, 1H), 8.23 (d, J=4.8 Hz, 1H). m/z (ESI) 227.1 (M+H)+.
Workup
- customa brown precipitate was obtained over a period of 30 minutes
- customAfter completion of reaction
- filtrationThe precipitate was filtered
- washwashed with Et2O (15 mL)
- customdried under vacuum
Sources & evidence
- ORD record
- ord-f9e8dfc801284a04ad88b5ec74bfd6a5
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340549B2
Reaction notes
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