4-bromo-1-ethenyl-2-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2.5 g (11.2 mmol) of 4-bromo-2-fluoro-1-vinylbenzene were reacted according to General Method 1A with 3.2 g (14.5 mmol) of [5-(methoxycarbonyl)pyridin-3-yl]boronic acid hydrochloride. The release of the hydrochloride was achieved by additional addition of 1.70 g (12.3 mmol) of potassium carbonate. Yield: 1.9 g (61% of theory)

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

Procedure: 10.0 g (49.3 mmol) of 4-bromo-2-fluorobenzaldehyde were dissolved in 40 ml of dichloromethane, admixed with 9.6 ml (9.7 g, 64.0 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene and 19.4 g (54.2 mmol) of methyltriphenylphosphonium bromide and stirred at RT for 3 h. The reaction mixture was purified on silica gel (eluent: dichloromethane). The product fractions were combined, concentrated under reduced pressure and dried under high vacuum. Yield: 4.5 g (41% of theory) The reaction mixture was purified on silica gel (eluent: dichloromethane) concentrated under reduced pressure dried under high vacuum

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

Procedure: 10.0 g (49.3 mmol) of 4-bromo-2-fluorobenzaldehyde were dissolved in 40 ml of dichloromethane, admixed with 9.6 ml (9.7 g, 64.0 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene and 19.4 g (54.2 mmol) of methyltriphenylphosphonium bromide and stirred at RT for 3 h. The reaction mixture was purified on silica gel (eluent: dichloromethane). The product fractions were combined, concentrated under reduced pressure and dried under high vacuum. Yield: 4.5 g (41% of theory) The reaction mixture was purified on silica gel (eluent: dichloromethane) concentrated under reduced pressure dried under high vacuum

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 4-Bromo-2-fluoro-1-vinyl-benzene (1.80 g, 8.96 mmol) was dissolved in ethyl acetate (50 mL) and palladium-on-carbon (10%, 70 mg) was added and the mixture was hydrogenated under 1 atmosphere overnight. The mixture was filtered and the filtrate was concentrated to give the crude, 1.80 g, which was used directly for the next step. was hydrogenated under 1 atmosphere overnight The mixture was filtered the filtrate was concentrated to give the crude, 1.80 g, which

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

Procedure: To a stirred suspension of 4-bromo-2-fluoro-benzaldehyde (Aldrich, 2.30 g, 11.3 mmol) and methyltriphenylphosphonium bromide(Aldrich, 4.93 g, 13.6 mmol) in ether (50 mL), potassium tert-butoxide(1.52 g, 13.6 mmol) was added and the mixture was stirred at room temperature for 1 hour. The solid was filtered off and the filtrate was concentrated. The residue was treated with 30% ethyl acetate/hexanes (3 mL) and the solid was removed by filtration. The filtrate was filtered through a silica gel pad eluting with 30% ethyl acetate/hexanes to give a yellow oil. 1.54 g, 68%. was added The solid was filtered off the filtrate was concentrated The residue was treated with 30% ethyl acetate/hexanes (3 mL) the solid was removed by filtration The filtrate was filtered through a silica gel pad eluting with 30% ethyl acetate/hexanes to give a yellow oil

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

Procedure: To a stirred suspension of 4-bromo-2-fluoro-benzaldehyde (Aldrich, 2.30 g, 11.3 mmol) and methyltriphenylphosphonium bromide(Aldrich, 4.93 g, 13.6 mmol) in ether (50 mL), potassium tert-butoxide(1.52 g, 13.6 mmol) was added and the mixture was stirred at room temperature for 1 hour. The solid was filtered off and the filtrate was concentrated. The residue was treated with 30% ethyl acetate/hexanes (3 mL) and the solid was removed by filtration. The filtrate was filtered through a silica gel pad eluting with 30% ethyl acetate/hexanes to give a yellow oil. 1.54 g, 68%. was added The solid was filtered off the filtrate was concentrated The residue was treated with 30% ethyl acetate/hexanes (3 mL) the solid was removed by filtration The filtrate was filtered through a silica gel pad eluting with 30% ethyl acetate/hexanes to give a yellow oil

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

Procedure: To a suspension of copper(I) trifluoromethanesulfonate benzene complex (0.01 eq) in chloroform (100 mL) at rt, was added (R,R)-2,2′-isopropylidene-bis(4-tert-butyl-2-oxazoline) (0.01 eq). The mixture was stirred at for 1 h then cannulated through glass wool in a solution of styrene from step 5 (1.2 eq) in chloroform (0.1M) at 4° C. To this solution was added a solution of ethyl diazoacetate (0.8 eq) in of chloroform (1M) dropwise over 3 h. The final mixture was stirred overnight at 4° C. The mixture was concentrated. Flash chromatography (Hexane, EtOAc; 95:5) afforded the desired compound. (84:16, trans:cis isomers, methodology described in Evans et al. J. Am. Chem. Soc. 1991, 113, 726) The mixture was concentrated

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

Procedure: To a suspension of methyltriphenylphosphonium bromide (1.1 eq) in tetrahydrofuran (0.13M) at −78° C., was added n-butyllithium (2.5M in hexanes, 1.1 eq) dropwise over 20 min. The reaction mixture was stirred at −78° C. for 15 min, warm to 0° C., stirred for 15 min and cooled back to −78° C. A solution of 4-bromo-2-fluoro-benzaldehyde (1 eq) in 100 mL THF was added dropwise over 30 min. Final mixture was allowed to warm slowly to rt and stirred for 1 h. The resulting mixture was quenched with a saturated NH4Cl solution and diluted with 2 volume of hexane. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The residue was diluted with Hexane/EtOAc (9:1) and filtered on a pad of Silica gel. The fractions were combined and concentrated to afford the desired material warm to 0° C. stirred for 15 min cooled back to −78° C to warm slowly to rt stirred for 1 h The resulting mixture was quenched with a saturated NH4Cl solution diluted with 2 volume of hexane The organic extract was washed with brine dried over MgSO4 filtered concentrated The residue was diluted with Hexane/EtOAc (9:1) filtered on a pad of Silica gel concentrated