C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[N:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17].[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br>O1CCCC1>[F:23][C:24]1[CH:25]=[C:26]([CH2:27][CH2:13][C:14]2[N:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16]([OH:18])=[O:17])[CH:29]=[CH:30][CH:31]=1Dissolve diisopropylamine (3.8 mL, 27.3 mmol) in dry tetrahydrofuran (75 mL). Chill the resulting mixture to −78° C. and add butyl lithium (1.6M solution in hexanes, 17.1 mL, 27.3 mmol). Warm the reaction mixture to 0° C. and add a fine slurry of 2-methyl-nicotinic acid (1.5 g, 10.9 mmol) in THF (25 mL) portionwise during 10 min. Stir the resulting slurry for 1 h, then add 3-fluorobenzyl bromide (2.0 mL, 16.4 mmol) and stir 5 min. Quench the reaction with water (100 mL). Extract the reaction mixture with diethyl ether (100 mL). Adjust the pH of the aqueous layer to 3.1 with concentrated aqueous hydrochloric acid solution. Treat the resulting slurry with ethyl acetate and stir to dissolve all solids. Separate the layers and extract the aqueous layer with ethyl acetate. Concentrate the combined extracts to dryness. LCMS (APCI-pos): 244.1 (M+H).
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