methyl 2-(2-chloro-4-hydroxyphenyl)acetate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of azetidin-1-yl-(7-chloro-thieno[3,2-b]pyridin-2-yl)-methanone (21a) (930 mg, 3.70 mmol), (2-chloro-4-hydroxy-phenyl)-acetic acid methyl ester (49e) (740 mg, 3.70 mmol), and Cs2CO3 (1.82 g, 7.40 mmol) in 7 mL of DMSO was heated at 100° C. for overnight and cooled to room temperature. EtOAc and water were added. The organic layer was washed three times with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography eluting with EtOAc:CHCl3:MeOH (1:1:0.04) to provide 640 mg of white solid as the intermediate 49f. 1H NMR (300 MHz, CD3OD) δ 8.47 (d, 1H, J=5.46 Hz), 7.74 (s, 1H), 7.43 (d, 1H, J=8.48 Hz), 7.32 (d, 1H, J=2.45 Hz), 7.15–7.10 (m, 1H), 6.73 (d, 1H, J=5.47 Hz), 4.67–4.54 (m, 2H), 4.24–4.13 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H), 2.48–2.33 (m, 2H). LCMS (ESI+) [M+H]/z Calc'd 417, found 417. cooled to room temperature The organic layer was washed three times with water dried over Na2SO4 concentrated in vacuo The residue was purified by flash column chromatography eluting with EtOAc:CHCl3:MeOH (1:1:0.04)