[NH2:1][C:2]1[C:3]([CH3:13])=[C:4]([CH:9]=[C:10]([Br:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[O:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O.C([O-])(O)=O.[Na+]>[Br:12][C:10]1[CH:11]=[C:2]([NH:1][CH:17]2[CH2:18][CH2:19][O:14][CH2:15][CH2:16]2)[C:3]([CH3:13])=[C:4]([CH:9]=1)[C:5]([O:7][CH3:8])=[O:6]A 1 L round-bottomed flask was charged with methyl 3-amino-5-bromo-2-methylbenzoate (15.26 g, 62.5 mmol) and dihydro-2H-pyran-4(3H)-one (9.39 g, 94 mmol) in 1,2-dichloroethane (DCE) (250 mL) to give a yellow solution at room temperature under nitrogen. Acetic acid (21.47 mL, 375 mmol) was added to the reaction mixture. After 30 min, sodium triacetoxyborohydride (39.8 g, 188 mmol) was added to the reaction mixture. After 3 h, sodium triacetoxyborohydride (39.8 g, 188 mmol) was added to the reaction mixture. The reaction was stirred overnight, at which time it was diluted with water and neutralized with NaHCO3 to pH 7. The reaction mixture was extracted with EtOAc (3×). The combined EtOAc layers were stirred with Na2SO4 and activated carbon darco for 30 min, then filtered through a pad of SiO2 (2″×1″) and concentrated. The solids were stirred with ether and filtered to obtain methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate (15.4 g, 46.9 mmol, 75% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.98 (d, J=2.02 Hz, 1 H), 6.94 (d, J=1.77 Hz, 1 H), 5.03 (d, J=8.08 Hz, 1 H), 3.94-3.84 (m, 2 H), 3.80 (s, 3 H), 3.64-3.51 (m, 1 H), 3.44 (td, J=11.68, 1.89 Hz, 2 H) 2.15 (s, 3 H), 1.84 (dd, J=12.63, 2.02 Hz, 2 H), 1.43-1.69 (m, 2 H). MS(ES) [M+H]+ 328, 330.
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