Diisopropylethylamine → methyl 6-(2,6-difluoro-4-((tetrahydro-2H-pyran-3-yl)oxy)phenyl)-5-fluoropicolinate
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([F:24])[C:14]=1B1OC(C)(C)C(C)(C)O1)[O:5][CH:6]1[CH2:11][CH2:10][CH2:9][O:8][CH2:7]1.Br[C:26]1[N:31]=[C:30]([C:32]([O:34][CH3:35])=[O:33])[CH:29]=[CH:28][C:27]=1[F:36].CCN(C(C)C)C(C)C>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:24][C:13]1[CH:12]=[C:4]([O:5][CH:6]2[CH2:11][CH2:10][CH2:9][O:8][CH2:7]2)[CH:3]=[C:2]([F:1])[C:14]=1[C:26]1[N:31]=[C:30]([C:32]([O:34][CH3:35])=[O:33])[CH:29]=[CH:28][C:27]=1[F:36]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 120 °C
Procedure
A mixture of 3-[3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]tetrahydro-2H-pyran (0.436 g, 1.28 mmol), methyl 6-bromo-5-fluoropyridine-2-carboxylate (0.300 g, 1.28 mmol) and DIPEA (0.67 mL, 3.8 mmol) in 1,4-dioxane (6 mL) and water (0.3 mL) was purged with nitrogen and then bis(tri-tert-butylphosphine)palladium (65.5 mg, 0.128 mmol) was added. The reaction mixture was sealed and heated at 120° C. for 40 min., then cooled and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes) to give methyl 6-[2,6-difluoro-4-(tetrahydro-2H-pyran-3-yloxy)phenyl]-5-fluoropyridine-2-carboxylate.
Workup
- customwas purged with nitrogen
- customThe reaction mixture was sealed
- temperaturecooled
- filtrationfiltered through a pad of diatomaceous earth
- concentrationThe filtrate was concentrated under reduced pressure
- customthe resulting residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-c929836889b94f22ae9066580b7c5c85
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09200004B2
Reaction notes
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