Potassium Carbonate → tert-butyl 6-(6-(methoxycarbonyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate

温度

90 °C

A mixture of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (53B) (72 mg, 0.20 mmol), methyl 6-bromo-3-(3-phenoxypropoxy)picolinate (26C) (72 mg, 0.20 mmol), K2CO3 (30 mg, 0.22 mmol in 0.5 mL of water), tetrabutyl ammonium bromide (64 mg, 0.20 mmol) and dichlorobis(triphenylphosphine)palladium (II) (10 mg, catalytic amount) in 1,4-dioxane (5 mL) was heated to 90° C. for 6 hours. The reaction mixture was cooled to rt, diluted with EtOAc, filtered through Celite, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with 20% EtOAc in hexanes to provide the desired product tert-butyl 6-(6-(methoxycarbonyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (53C). 1H NMR (300 MHz, CDCl3): 8.49 (1H, s), 7.74 (1H, d), 7.60 (1H, d), 7.38 (1H, d), 7.24 (2H, m), 6.90 (4H, m), 4.31 (2H, t), 4.18 (2H, t), 4.25 (2H, t), 3.95 (3H, s), 3.85 (2H, t), 2.3 (2H, m), 1.58 (9H, s). LCMS (APCI): m/z 521.1 (M+H).

1. temperatureThe reaction mixture was cooled to rt
2. filtrationfiltered through Celite
3. concentrationconcentrated under reduced pressure
4. customThe crude material was purified by column chromatography on silica gel eluting with 20% EtOAc in hexanes

ORDレコード

ord-29f8eb80881141288d766acc8725d3bd

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08518970B2