Hydrogen Bromide → 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:15][CH3:16])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2C(OC)=O)[CH:7]=1.BrC1C2N(N=CC=2C(OC)=O)C=C(OC)C=1.Br.[OH-].[Na+]>C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:15][CH3:16])[C:5]2[N:6]([N:8]=[CH:9][CH:10]=2)[CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of methyl 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (4.33 g, 15.2 mmol) and methyl 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (1.44 g, 5.05 mmol) was suspended in hydrobromic acid (100 ml, 884 mmol) and heated to 100° C. for 60 minutes. The mixture was cooled to 0° C. and carefully quenched via the addition of 1N aqueous sodium hydroxide (152 ml, 909 mmol). The reaction mixture was diluted in ethyl acetate, washed with 1N aqueous sodium hydroxide and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (Ethyl acetate/isohexane gradient) to give 6-bromo-4-methoxypyrazolo[1,5-a]pyridine (faster eluting isomer) and 4-bromo-6-methoxypyrazolo[1,5-a]pyridine (slower eluting isomer).
Workup
- temperatureThe mixture was cooled to 0° C.
- washwashed with 1N aqueous sodium hydroxide and brine
- dry with materialthen dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by column chromatography on silica gel (Ethyl acetate/isohexane gradient)
Sources & evidence
- ORD record
- ord-79c3fa0785554c43861c5c6594a72f5d
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08455477B2
Reaction notes
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