61.6% |
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In toluene at 90℃; for 19h; Inert atmosphere; |
1 Step-1: Preparation of ethyl 2-(2-methoxy-4-(methoxycarbonylamino)phenyl)acetate (19b)
To a degassed solution of ethyl 2-(4-bromo-2-methoxyphenyl)acetate (19a) (750 mg, 2.75 mmol; CAS1261570-38-0) in toluene (30 mL) was added dicyclohexyl(2',4',6'- triisopropylbiphenyl-2-yl)phosphine (131 mg, 0.275 mmol), methyl carbamate (309 mg, 4.12 mmol), Pd2(dba)3 (126 mg, 0.137 mmol), cesium carbonate (895 mg, 2.75 mmol) and heated under nitrogen at 90 °C for 19 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water (60 mL), brine (60 mL), dried, filtered and concentrated in vacuum. The residue obtained was purified by flash column chromatography (silica gel (24g), eluting with 0 to 25% ethyl acetate in hexanes) to give ethyl 2-(2-methoxy-4- (methoxycarbonylamino)phenyl)acetate (19b) (452 mg, 61.6 % yield) as a yellow solid; NMR (300 MHz, DMSO-7e) d 9.62 (s, 1H), 7.20 - 7.17 (m, 1H), 7.05 (d, J= 8.1 Hz, 1H), 6.94 (dd, J= 8.1, 2.0 Hz, 1H), 4.04 (q, 7= 7.1 Hz, 2H), 3.70 (s, 3H), 3.66 (s, 3H), 3.49 (s, 2H), 1.16 (t, J= 7.1 Hz, 3H); MS (ES+): 268.1 (M+l) |