benzyl pent-4-ynoate

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:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add bis(triphenylphosphine)palladium(II) chloride (0.14 g; 0.1 equiv; 0.20 mmoles) and copper(I) iodide (0.039 mg; 0.1 equiv; 0.20 mmoles) to a deoxygenated solution of 4-iodo-1H-imidazole (0.388 g; 1.0 equiv; 2.00 mmoles), benzyl pent-4-ynoate (0.376 g; 1.0 equiv; 2.00 mmoles), and triethylamine (0.84 mL; 3 equiv; 6.0 mmoles) in dimethylformamide (8 mL). Heat the mixture to 75° C. for 16 hours, then dilute the mixture with water (30 mL) and extract 3× with ethyl acetate. Wash the combined organic extracts with brine, dry over magnesium sulfate, filter, and concentrate to provide the crude product. Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane) to afford benzyl 5-(1H-imidazol-5-yl)pent-4-ynoate (0.35 g; 69%) as a colorless oil: MS (m/z): 255(M+1). extract 3× with ethyl acetate Wash the combined organic extracts with brine dry over magnesium sulfate filter concentrate to provide the crude product Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane)

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

Procedure: In analogy to the procedure described for example 8 a], pent-4-ynoic acid benzyl ester (Rosowsky, Andre; Forsch, Ronald A.; Queener, Sherry F., Journal of Medicinal Chemistry (2003), 46(9), 1726-1736) was reacted with 4-iodobenzotrifluoride in the presence of PdCl2(Ph3P)2 and cuprous iodide to give the title compound as yellow oil.

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

Procedure: To a degassed (Ar) solution of 1-iodo-3-trifluoromethoxy-benzene (0.54 ml, 3 mmol) in acetonitrile (30 ml) was added pent-4-ynoic acid benzyl ester (719 mg, 4 mmol; A. Rosowsky, R. A. Forsch, F. S. Queener, J. Med. Chem. 2003, 46, 1726-1736), PdCl2(Ph3P)2 (122 mg, 0.17 mmol), cuprous iodide (33 mg, 0.17 mmol) and triethylamine (1.45 ml, 10 mmol). The reaction mixture was stirred for 2.5 h at ambient temperature, poured into a solution of aqueous 10% KHSO4/ice water 1/1 and extracted two times with ether. The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (silica gel, heptane/AcOEt) to give 1.13 g (3.2 mmol, 93%) of the title compound as yellow oil. extracted two times with ether The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl dried over sodium sulfate The solvent was removed under reduced pressure the residue purified by flash chromatography (silica gel, heptane/AcOEt)

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

Procedure: To a degassed (Ar) solution of 1-iodo-3-trifluoromethoxy-benzene (0.54 ml, 3 mmol) in acetonitrile (30 ml) was added pent-4-ynoic acid benzyl ester (719 mg, 4 mmol; A. Rosowsky, R. A. Forsch, F. S. Queener, J. Med. Chem. 2003, 46, 1726-1736), PdCl2(Ph3P)2 (122 mg, 0.17 mmol), cuprous iodide (33 mg, 0.17 mmol) and triethylamine (1.45 ml, 10 mmol). The reaction mixture was stirred for 2.5 h at ambient temperature, poured into a solution of aqueous 10% KHSO4/ice water 1/1 and extracted two times with ether. The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (silica gel, heptane/AcOEt) to give 1.13 g (3.2 mmol, 93%) of the title compound as yellow oil. extracted two times with ether The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl dried over sodium sulfate The solvent was removed under reduced pressure the residue purified by flash chromatography (silica gel, heptane/AcOEt)

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

Procedure: A mixture of Example 510B (8.7017 g, 46.23 mmol), tributyltin hydride (14.5 mL, 54.09 mmol), and AIBN (228 mg, 1.39 mmol) was stirred at 80° C. for 24 hours, cooled to room temperature, and purified by flash column chromatography to provide the desired product (16.4529 g, 74%). 1H NMR (300 MHz, DMSO-d6) δ 7.35 (m, 5H), 5.93 (m, 1H), 5.09 (m, 1H), 5.07 (s, 2H), 2.44 (m, 2H), 2.38 (m, 2H), 1.45 (m, 6H), 1.25 (m, 6H), 0.85 (m, 15H). purified by flash column chromatography

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

Procedure: A solution of 4-pentynoic acid (5.25 g, 53.5 mmol) in DMF (107 mL) was treated with K2CO3 (11.09 g, 80.3 mmol) and benzyl bromide (6.37 mL, 53.5 mmol), stirred for 24 hours, diluted with water (200 mL), and extracted with diethyl ether (3×150 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography to provide the desired product (10.07 g, 100%). MS (ESI(+)) m/e 206 (M+NH4)+; 1H NMR (300 MHz, DMSO-d6) δ 7.37 (m, 5H), 5.12 (s, 2H), 2.61 (t, 1H), 2.57 (m, 2H), 2.42 (m, 2H). extracted with diethyl ether (3×150 mL) The combined organic extracts were dried (MgSO4) filtered concentrated The residue was purified by flash chromatography

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

Procedure: To a solution in dichloromethane (25 mL) containing a few drops DMF of 4-pentynoic acid (2.49 g, 23.4 mmol) was added oxalyl chloride (2.2 mL, 25 mmol). The reaction mixture was stirred for 1.5 hours and benzyl alcohol (3.9 mL, 38 mmol) was added via syringe. The reaction mixture was stirred for 6 hours and then was extracted with saturated aqueous sodium carbonate. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo to give 4-pentynoic acid benzyl ester (5.94 g) as a yellow liquid. The reaction mixture was stirred for 6 hours was extracted with saturated aqueous sodium carbonate The organic phase was dried over MgSO4 filtered concentrated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add bis(triphenylphosphine)palladium(II) chloride (0.14 g; 0.1 equiv; 0.20 mmoles) and copper(I) iodide (0.039 mg; 0.1 equiv; 0.20 mmoles) to a deoxygenated solution of 4-iodo-1H-imidazole (0.388 g; 1.0 equiv; 2.00 mmoles), benzyl pent-4-ynoate (0.376 g; 1.0 equiv; 2.00 mmoles), and triethylamine (0.84 mL; 3 equiv; 6.0 mmoles) in dimethylformamide (8 mL). Heat the mixture to 75° C. for 16 hours, then dilute the mixture with water (30 mL) and extract 3× with ethyl acetate. Wash the combined organic extracts with brine, dry over magnesium sulfate, filter, and concentrate to provide the crude product. Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane) to afford benzyl 5-(1H-imidazol-5-yl)pent-4-ynoate (0.35 g; 69%) as a colorless oil: MS (m/z): 255(M+1). extract 3× with ethyl acetate Wash the combined organic extracts with brine dry over magnesium sulfate filter concentrate to provide the crude product Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane)

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

Procedure: In analogy to the procedure described for example 8 a], pent-4-ynoic acid benzyl ester (Rosowsky, Andre; Forsch, Ronald A.; Queener, Sherry F., Journal of Medicinal Chemistry (2003), 46(9), 1726-1736) was reacted with 4-iodobenzotrifluoride in the presence of PdCl2(Ph3P)2 and cuprous iodide to give the title compound as yellow oil.