Ethyl chloroformate → Ethyl 3-bromo-5-fluoropyridine-4-carboxylate
Reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C(NC(C)C)(C)C.[Li].Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19]>C1COCC1.CCOC(C)=O>[CH2:21]([O:20][C:18](=[O:19])[C:7]1[C:6]([F:8])=[CH:5][N:4]=[CH:3][C:2]=1[Br:1])[CH3:22]Participants
6
Conditions
- Temperature
- -78 °C
Procedure
To a round bottom flask is added 3-bromo-5-fluoropyridine (475 mg, 2.7 mmol) in 4 ml of dry THF at −78° C., followed by the addition of lithium diisopropylamine (1.62 ml, 3.24 mmol). The reaction mixture is stirred at −78° C. for 1 hour, followed by the addition of ethyl chloroformate (586 mg, 5.4 mmol). The reaction mixture is warmed up to room temperature and stirred for 1 hour. The reaction mixture is diluted with EtOAc, washed with saturated NH4Cl/water, brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product. Purification by the flash column chromatography affords 670 mg of 3-bromo-5-fluoro-isonicotinic acid ethyl ester.
Workup
- temperatureThe reaction mixture is warmed up to room temperature
- stirringstirred for 1 hour
- washwashed with saturated NH4Cl/water, brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customto give the crude product
- customPurification by the flash column chromatography
Sources & evidence
- ORD record
- ord-fac97b632094485f873b8fd58e74fde4
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181272B2
Reaction notes
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