methyl 4-bromofuran-2-carboxylate

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

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

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2-furancarboxylate (1.0 g, 4.88 mmol) in THF (20 mL) was added aqueous Na2CO3(2N, 8 mL, 16 mmol.), PdCl2(dppf) (0.35 g, 0.49 mmol) and 1-ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.3 g, 5.85 mmol). The reaction mixture was heated to 70° C. in a sealed tube. After 2 h, the reaction mixture was concentrated under vacuum and purified on silica (EtOAc/Hex, 20-40%) to afford the title compound (0.8 g, 74.5%) as a light yellow solid: LC-MS (ES) m/z=221 (M+H)+. the reaction mixture was concentrated under vacuum purified on silica (EtOAc/Hex, 20-40%)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2-furancarboxylate (1.0 g, 4.88 mmol) in THF (20 mL) was added aqueous Na2CO3(2N, 8 mL, 16 mmol.), PdCl2(dppf) (0.35 g, 0.49 mmol) and 1-ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.3 g, 5.85 mmol). The reaction mixture was heated to 70° C. in a sealed tube. After 2 h, the reaction mixture was concentrated under vacuum and purified on silica (EtOAc/Hex, 20-40%) to afford the title compound (0.8 g, 74.5%) as a light yellow solid: LC-MS (ES) m/z=221 (M+H)+. the reaction mixture was concentrated under vacuum purified on silica (EtOAc/Hex, 20-40%)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2-furancarboxylate (500 mg, 2.439 mmol) in THF (5 mL) was added aqueous Na2CO3 (2N, 3.6 mL, 7.2 mmol), PdCl2(dppf) (160 mg, 0.22 mmol), and 1-ethyl-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (700 mg, 2.96 mmol). The reaction mixture was heated to 70° C. in a sealed tube. After 2 h, the reaction mixture was concentrated under vacuum and purified on silica (EtOAc/Hex, 20-40%) to afford the title compound (460 mg, 76%) as a light yellow solid: LC-MS (ES) m/z 235 (M+H)+. the reaction mixture was concentrated under vacuum purified on silica (EtOAc/Hex, 20-40%)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2-furancarboxylate (500 mg, 2.439 mmol) in THF (5 mL) was added aqueous Na2CO3 (2N, 3.6 mL, 7.2 mmol), PdCl2(dppf) (160 mg, 0.22 mmol), and 1-ethyl-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (700 mg, 2.96 mmol). The reaction mixture was heated to 70° C. in a sealed tube. After 2 h, the reaction mixture was concentrated under vacuum and purified on silica (EtOAc/Hex, 20-40%) to afford the title compound (460 mg, 76%) as a light yellow solid: LC-MS (ES) m/z 235 (M+H)+. the reaction mixture was concentrated under vacuum purified on silica (EtOAc/Hex, 20-40%)

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

Procedure: A solution of methyl 4-bromo-2-furancarboxylate (470 mg, 2.29 mmol), potassium carbonate (1584 mg, 11.46 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (525 mg, 2.52 mmol)[prepared according to Preparation 7] and bis-(tri-t-butylphosphine)Palladium (0) (58.6 mg, 0.12 mmol) in 1,4-dioxane (9.55 ml) and water (1.9 ml) was stirred at 80° C. After 1 hr, the solution was partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (30% EtOAc in hexanes) affording the title compound (124 mg, 0.60 mmol, 26% yield) as a white powder: LCMS (ES) m/e 206 (M+H)+. the solution was partitioned between H2O-DCM the aqueous phase was washed several times with DCM The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (30% EtOAc in hexanes)

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

Procedure: A solution of methyl 4-bromo-2-furancarboxylate (1.4 g, 6.83 mmol) and NCS (0.912 g, 6.83 mmol) in N,N-dimethylformamide (13.7 ml) was stirred in a sealed tube for 1 h at 100° C. After 1 h, the solution was partitioned between DCM-H2O and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (2-10% EtOAc in hexanes) affording methyl 4-bromo-5-chloro-2-furancarboxylate (1.348 g, 5.12 mmol, 75% yield) as a white solid: LCMS (ES) m/e 238, 240, 242 (M, M+2, M+4)+. the solution was partitioned between DCM-H2O the aqueous phase was washed several times with DCM The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (2-10% EtOAc in hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4,5-dibromo-2-furancarboxylate (3.3 g, 11.62 mmol) in tetrahydrofuran (46 ml) at −40° C. was added isopropylmagnesium chloride (6.97 ml, 13.95 mmol). After 1 h, Water (11 ml) was added and the solution warmed to 25° C. The reaction mixture was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified by column chromatography (3% EtOAc in hexanes) affording methyl 4-bromo-2-furancarboxylate (1.4 g, 6.49 mmol, 56% yield) as a yellow solid: LCMS (ES) m/e 205, 207 (M, M+2)+. The reaction mixture was then partitioned between H2O-DCM the aqueous phase was washed several times with DCM The combined organic fractions were dried over Na2SO4 concentrated purified by column chromatography (3% EtOAc in hexanes)

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

Procedure: A solution of methyl 4-bromo-2-furancarboxylate (470 mg, 2.29 mmol), potassium carbonate (1.58 g, 11.46 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (525 mg, 2.52 mmol)[prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (58.6 mg, 0.115 mmol) in 1,4-Dioxane (9.5 ml) and water (1.9 ml) was stirred at 80° C. in a sealed tube for 1 h. The solution was partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (30% EtOAc in hexanes) affording methyl 4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylate (124 mg, 0.60 mmol, 26% yield) as a white powder: LCMS (ES) m/e 206 (M+H)+. The solution was partitioned between H2O-DCM the aqueous phase was washed several times with DCM The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (30% EtOAc in hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4,5-dibromo-2-furancarboxylate (1 g, 3.52 mmol) in tetrahydrofuran (14.1 ml) at −40° C. was added isopropylmagnesium chloride (1.85 ml, 3.70 mmol). After 2 h, H2O (3.52 ml) was added and the solution warmed to 25° C. The reaction mixture was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified by column chromatography (3% EtOAc in hexanes) affording methyl 4-bromo-2-furancarboxylate (470 mg, 2.04 mmol, 58% yield) as a white solid: LCMS (ES) m/e 204, 206 (M, M+2)+. The reaction mixture was then partitioned between H2O-DCM the aqueous phase was washed several times with DCM The combined organic fractions were dried over Na2SO4 concentrated purified by column chromatography (3% EtOAc in hexanes)