Reaction equation
Cl[C:2]1[CH:3]=[C:4]([F:9])[C:5]([F:8])=[N:6][CH:7]=1.[CH3:10][C:11]1[CH:15]=[C:14]([Sn](CCCC)(CCCC)CCCC)[O:13][N:12]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCOCC1>>[F:8][C:5]1[C:4]([F:9])=[CH:3][C:2]([C:14]2[O:13][N:12]=[C:11]([CH3:10])[CH:15]=2)=[CH:7][N:6]=1Participants
5
Conditions
- Temperature
- 100 °C
Procedure
A 330 mL pressure vessel was charged with 5-chloro-2,3-difluoropyridine (5.00 g, 33.4 mmol), 3-methyl-5-(tributylstannyl)isoxazole (14.9 g, 40.1 mmol), XPhos (2.23 g, 4.68 mmol), PdOAc2 (0.526 g, 2.34 mmol), and 1,4-dioxane (167 ml, 33.4 mmol), flushed with argon, sealed, then heated at 100° C. for 16 hours. The mixture was concentrated; the black oil was absorbed onto silica gel and purified by MPLC, eluting with 20% EtOAc in hexanes isocratic to yield an orange solid; this was triturated with hexanes to give 2,3-difluoro-5-(3-methylisoxazol-5-yl)pyridine (3.6278 g, 55.3% yield) as a yellow solid.
Workup
- customflushed with argon
- customsealed
- concentrationThe mixture was concentrated
- customthe black oil was absorbed onto silica gel
- custompurified by MPLC
- washeluting with 20% EtOAc in hexanes isocratic
- customto yield an orange solid
- customthis was triturated with hexanes
Sources & evidence
- ORD record
- ord-cb12bebbeccc4a719bb91e95332a4562
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08198448B2
Linked notes
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