Trifluoroacetic acid → 7-bromo-1-fluoro-5-methylene-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridine
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:20](=[CH:21][CH:22]=1)[O:19][C:7]1[C:8]([F:18])=[N:9][C:10]([O:12][CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:11][C:6]=1[C:5]2=O.[CH3:24][Si](C[Li])(C)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:20](=[CH:21][CH:22]=1)[O:19][C:7]1[C:8]([F:18])=[N:9][C:10]([O:12][CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:11][C:6]=1[C:5]2=[CH2:24]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a suspension of 7-bromo-1-fluoro-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridin-5-one (1000 mg, 2.63 mmol) in THF (25 mL) at −40° C. was added drop wise ((trimethylsilyl)methyl)lithium (1.0M solution in pentane; 3.95 mL, 3.95 mmol). After 10 min, TFA (0.304 mL, 3.95 mmol) was added drop wise and the reaction mixture was allowed to warm to rt Additional 1 ml of TFA was added and the reaction mixture was allowed to stir for 1 hour at P. An aqueous, saturated K2CO3 solution was added, followed by EtOAc. The organic phase was separated and dried over Na2SO4. The solvent was removed under reduced pressure to yield 7-bromo-1-fluoro-5-methylene-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridine as a yellow solid (995 mg), which was used in the next step without further purification.
Workup
- additionwas added
- customThe organic phase was separated
- dry with materialdried over Na2SO4
- customThe solvent was removed under reduced pressure
Sources & evidence
- ORD record
- ord-6a1f2ab54c0b45cf8efea7258651c1cb
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08497264B2
Reaction notes
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