Reaction equation
CN(CCN(C)C)C.C([Li])(CC)C.[F:14][C:15]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].CN([CH:28]=[O:29])C>C1COCC1>[F:14][C:15]1[C:23]([CH:28]=[O:29])=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]Participants
Conditions
- Temperature
- -75 °C
Procedure
A solution of TMEDA (10.5 mL, 70 mmol) in THF (50 mL) was cooled to <−80° C. and treated with sec-butyllithium (50 mL, 70 mmol). A solution of 2,4-difluorobenzoic acid (5.0 g, 31.6 mmol) in THF was added dropwise maintaining the temperature below −80° C. The reaction mixture was allowed to warm to −75° C. and treated with DMF (15 mL), the mixture then allowed to warm to 0° C. before quenching the reaction with water. The aqueous layer was separated, acidified to pH ˜2 (concentrated HCl) and extracted twice with diethyl ether. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. The crude product was crystallized from cyclohexane/diethyl ether to give the title compound as a yellow solid (670 mg, 11%). 1H NMR (CDCl3, 400 MHz) 10.40 (1 H, s), 8.31 (1 H, ddd, J=8.96, 8.02, 6.08 Hz), 7.12 (1 H, td, J=9.09, 1.42 Hz).
Workup
- temperaturemaintaining the temperature below −80° C
- temperatureto warm to 0° C.
- custombefore quenching
- customthe reaction with water
- customThe aqueous layer was separated
- extractionextracted twice with diethyl ether
- dry with materialThe combined organic extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give a yellow oil
- customThe crude product was crystallized from cyclohexane/diethyl ether
Sources & evidence
- ORD record
- ord-a47cc2a286804b1e87ac2eff419cddd0
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08841462B2
Linked notes
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