| 62% |
With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In N,N-dimethyl-formamide; at 80 - 85℃;Inert atmosphere; |
Add tris(dibenzylideneacetone)dipalladium(0) (3.98 g, 4.35 mmol), tricyclohexylphosphine (2.44 g, 8.7 mmol) and potassium acetate (42.65 g, 435 mmol) to a solution of bis(pinacolato) diboron (35.88 g, 141.3 mmol) in dimethylformamide (175 mL). Bubbling N2 into the mixture for 15 minutes, then heat it to 80~85 C. Then add ethyl 5-bromonicotinate (25.0 g, 108.8 mmol) in dimethylformamide (75 mL) slowly to the mixture at 80~85 C., and stir the formed mixture at 80~85 C. for 4-5 hours. Cool the reaction mixture to 15-35 C., and then add methyl tertiary butyl ether (250 mL) and water (250 mL). Filter the mixture with diatomite and separate the organic and aqueous layers. Back extract the aqueous layer with methyl tertiary butyl ether (250 mL). Wash the combined organic layer with brine (150 mL) and water (150 mL). Concentrate the organic under vacuum, re-crystallize the crude product with methyl tertiary butyl ether/heptane (1:6), and then dry it below 55 C. to give the title compound as a grey solid (18.67 g, 62%). 1H NMR (acetone-d6, 400 MHz) delta40-1.43 (m, 15H), 4.44 (q, J=7.1 Hz, 2H), 8.57 (t, J=1.9 Hz, 1H), 9.02 (d, J=1.5 Hz, 1H), 9.225 (d, J=2.3 Hz, 1H) |
| 1.5 g |
With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; tricyclohexylphosphine tetrafluoroborate; In 1,4-dioxane; at 80 - 100℃; for 16h;Inert atmosphere; |
To a solution of 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl(1,3,2-dioxaborolan-2- yl))-1,3,2-dioxaborolane (1.54 g, 6.09 mmol) and tricyclohexylphosphonium tetrafluoroborate (0.1 12 g, 0.304) in 1,4-dioxane (20 mL) at ambient temperature was added KOAc (1.71 g, 17.4 mmol) and the reaction mixture was purged with nitrogen gas for 10 min. The reaction mixture was heated to 80 C. Pd2(dba)3 (0.199 g, 0.217 mmol) was added to the reaction mixture and the resulting reaction mixture purged with nitrogen for 10 min at 80 C. The reaction mixture was heated to 90 C and a solution of ethyl 5- bromonicotinate (1.00 g, 4.35 mmol) in 1,4-dioxane (5 mL) was added. The resulting mixture was stirred at 100 C for 16 h. The reaction mixture was allowed to cool to ambient temperature, filtered through CELITE and the filtrate was concentrated under reduced pressure to obtain ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (1.50 g). The residue was taken to the next step without further purification. LCMS (Condition 11): retention time 0.52 min, [M+1] = 196.1. 1H NMR (400 MHz, DMSO-d6) delta 1.16 (s, 12 H), 1.35 (t, J= 7.2 Hz, 3 H), 4.36 (q, J= 7.2 Hz, 2 H), 8.43 (dd, J= 1.6 Hz, J = 2.0 Hz, 1 H), 8.95 (d, J= 1.6 Hz, 1 H), 9.16 (br s, 1 H). |
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With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; tricyclohexylphosphine tetrafluoroborate; In 1,4-dioxane; at 80 - 100℃; for 16h;Inert atmosphere; |
To the solution of 4,4,5, 5-tetramethyl-2-(4,4,5, 5-tetramethyl(l, 3,2-dioxaborolan- 2-yl))-l,3,2-dioxaborolane (1.54 g, 6.09 mmol) and tricyclohexylphosphonium tetrafluoroborate (0.1 12 g, 0.304) in 1,4-dioxane (20 mL) at ambient temperature was added potassium acetate (1.71 g, 17.4 mmol) and the reaction mixture was purged with nitrogen gas for 10 min. The reaction mixture was heated to 80 C. Pd2(dba)3 (0.199 g, 0.217 mmol) was added to the reaction mixture and again nitrogen was passed through for the next 10 min at 80 C. The reaction mixture was heated to 90 C and a solution of ethyl 5-bromonicotinate (1.00 g, 4.35 mmol) in 1,4-dioxane (5 mL) was added. The resulting mixture was stirred at 100 C for 16 h. The reaction mixture was allowed to cool to ambient temperature, filtered through CELITE and the filtrate was concentrated under reduced pressure to obtain ethyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)nicotinate (1.5 g). The residue was taken to the next step without further purification. LCMS (Condition 5): retention time 0.52 min, [M+l] = 196.1. XH NMR (400 MHz, DMSO-d6) delta 1.16 (s, 12 H), 1.35 (t, J= 7.2 Hz, 3 H), 4.36 (q, J= 7.2 Hz, 2 H), 8.43 (dd, J = 1.6 Hz, J= 2.0 Hz, 1 H), 8.95 (d, J= 1.6 Hz, 1 H), 9.16 (br s, 1 H). |
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