4-FLUORO-2-METHYLBENZYL BROMIDE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from methyl 2-(tert-butoxy)-2-(6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 1-(bromomethyl)-4-fluoro-2-methylbenzene in a manner similar to that described in Example 25 as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) d=7.65 (d, J=7.0 Hz, 1 H), 7.41 (d, J=7.0 Hz, 1 H), 7.37-7.30 (m, 2 H), 7.03 (dd, J=6.0, 8.3 Hz, 1 H), 6.96-6.83 (m, 3 H), 6.22 (d, J=3.5 Hz, 1 H), 5.58-5.49 (m, 2 H), 5.44-5.37 (m, 1 H), 2.76 (s, 3 H), 2.47 (s, 3 H), 2.32 (s, 3 H), 0.95 (s, 9 H); LCMS (m/z) ES+=475 (M+1).

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Step (c) (S)-Di-tert-butyl 5-oxopyrrolidine-1,2-dicarboxylate (1.15 g, 4.0 mmol) was dissolved in dry THF (20 mL) and the solution was cooled to −78° C. A solution of LiHMDS (1M in hexanes, 4.4 mL, 4.4 mmol) then was added dropwise under nitrogen. The mixture was cooled at −78° C. for 40 minutes and then a solution of 2-methyl-4-fluorobenzyl bromide (975 mg, 4.8 mmol) in THF (5 mL) was added slowly. The mixture was stirred at −78° C. for 2 hours and then quenched with saturated ammonium chloride (20 mL). The mixture was extracted with diethyl ether (3×70 mL) and the combined extract was washed with brine (30 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Product was purified from the residue by flash column (eluted with a 4:1 hexanes/diethyl ether mixture) to give (2S,4R)-di-tert-butyl 4-(4-fluoro-2-methylbenzyl)-5-oxopyrrolidine-1,2-dicarboxylate (810 mg, 2.0 nmol, 49.7%), clean as a white solid. The mixture was cooled at −78° C. for 40 minutes quenched with saturated ammonium chloride (20 mL) The mixture was extracted with diethyl ether (3×70 mL) the combined extract was washed with brine (30 mL) dried over anhydrous sodium sulfate concentrated in vacuo Product was purified from the residue by flash column ( eluted with a 4:1 hexanes/diethyl ether mixture)