tert-butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholine-4-carboxylate synthesis

Yield:1131220-85-3 83%

Reaction Conditions:

with potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride in N,N-dimethyl-formamide at 80; for 3 h;

Steps:

4.4-6

A mixture of 2-(4-bromo-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (intermediate 34. 6 g, 17.5 mmol), bis(pinacolato)diboron (5.1 g, 20 mmol), potassium acetate (3.5 g, 36 mmol) and [l,l'-bis(diphenylphosphino)ferrocene] dichloropalladium(Il) (1.2 g, 1.5 mmol) in N,N-dimethylformamide (40 ml) was heated to 80 C under nitrogen atmosphere. After stirring for 3 hours, the reaction mixture was cooled to room temperature and poured into water. Extractive workup was performed with ethyl acetate and the organic phase was washed with brine. The collected organic layer was dried over sodium sulfate and concentrated. The resulting material was purified by flash column chromatography on silica gel (hexane/ethyl acetate = 5/1 as an eluent). 2-[4-(4,4,5,5-tetramethyl- [l,3,2]dioxaborolan-2-yl)-phenyl]-morpholine-4-carboxylic acid ?er?-bntyl ester (intermediate 35_, 5.6 g, 14.5 mmol, 83% yield) was obtained as a white solid.? NMR (400 MHz, CDCl3) ? : 1.34 (12H, s), 1.48 (9H, s), 2.80 (IH, br), 3.05 (lH, br), 3.68 (IH, dt, J=2.3, 11.7 Hz), 3.94 (2H, br), 4.03 (IH, d, J=10.4 Hz), 4.43 (IH, d, J=9.8 Hz), 7.38 (2H, d, J=7.9 Hz), 7.81 (2H, d, J=7.9 Hz) MS: [M+H]+ = 290 (? f?r^butoxycarbonyl) Melting point : 129.4 C

References:

WO2009/35159,2009,A1 Location in patent:Page/Page column 28; 31-32