4-FLUORO-3,5-DIMETHYLBENZYL BROMIDE

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (−78° C.) solution of (R)-4-benzyl-3-pent-4-enoyl-oxazolidin-2-one (0.500 g, 1.928 mmol) in 15 mL of THF, was added LiHMDS (2.9 mL, 2.9 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (0.460 g, 2.121 mmol) in 5 mL of THF was added. After being stirred at −78° C. for 1 h followed by warming to room temperature over 2 h, the reaction mixture was quenched with 50 mL of aqueous NH4Cl solution and extracted with dichloromethane (50 mL×3). The combined organic extracts were dried, filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (0.221 g, 56% yield). GC-MS: tR=7.0 min; m/z 395 (M+). After being stirred at −78° C. for 1 h by warming to room temperature over 2 h the reaction mixture was quenched with 50 mL of aqueous NH4Cl solution extracted with dichloromethane (50 mL×3) The combined organic extracts were dried filtered concentrated under reduced pressure The product was isolated by Flash column chromatography (silica gel) eluting with 0-100% dichloromethane/hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (−78° C.) solution of (R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one (0.220 g, 0.532 mmol) in 5 mL of THF, was added LiHMDS (0.80 mL, 0.80 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (0.346 g, 1.596 mmol) in 3 mL of THF was added. After stirring at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 20 mL of NH4Cl solution and extracted with dichloromethane (20 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (0.106 g, 36% yield). GC-MS: tR=15.6 min; m/z 549 (M+). After stirring at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h quenched with 20 mL of NH4Cl solution extracted with dichloromethane (20 mL×3) The combined organic extracts were dried (Na2SO4) filtered concentrated under reduced pressure The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (−78° C.) solution of (R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one (2.000 g, 6.071 mmol) in 40 mL of THF, was added LiHMDS (9.1 mL, 9.1 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (1.450 g, 6.678 mmol) in 10 mL of THF was added. After being stirred at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 80 mL of NH4Cl solution and extracted with dichloromethane (60 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (1.925 g, 68% yield). GC-MS: tR=8.8 min; m/z 465 (M+). After being stirred at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h quenched with 80 mL of NH4Cl solution extracted with dichloromethane (60 mL×3) The combined organic extracts were dried (Na2SO4) filtered concentrated under reduced pressure The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes