Yield:887581-65-9 48%

Reaction Conditions:

with hexamethylenetetramine in ethyl acetate at 20; for 1.5 h;

Steps:

35.3 Example 35, Step 3: (4-Chloro-2-(methylsulfonyl)phenyl)methanamine

Hexamethylenetetramine (40.8 g, 0.291 mol) was added in one portion to a stirred, room temperature solution of 1 -(bromomethyl)-4-chloro-2-(methylsulfonyl)benzene (75 g, 0.264 mol) in EtOAc (1 L). After 1 .5 h. the mixture was chilled in ice and the precipitate filtered, washed with cold EtOAc and air dried. This material was suspended in MeOH (375 mL), concentrated HCI (150 mL) added dropwise over 0.33 h. and the mixture heated at 40°C for 2 h. The mixture was cooled, concentrated under reduced pressure and the residue basified with 5M NaOH, with cooling, and extracted with dichloromethane (3 x 500 mL). Combined extracts were dried (MgS0₄) and evaporated and the residue chromatographed on silica gel eluting with 20 - 100 % EtOAc in isohexane gradient followed by 0 - 10 % MeOH containing 7N NH₃ in EtOAc gradient to afford the title compound as a pale brown solid (27.8 g, 48 %). 1 H NMR (400 MHz, CDCI₃): 8.02 (1 H, d), 7.58 (1 H, dd), 7.51 (1 H, d), 4.19 (2H, s), 3.23 (3H,s), 1 .64 (2H, s).

References:

WO2017/55860,2017,A1 Location in patent:Page/Page column 207; 208