Yield: 84%

Reaction Conditions:

with triethylamine in tetrahydrofuran at 0 - 20; for 2 h;Inert atmosphere;

Steps:

1 INTERMEDIATE B: tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzyl)piperazine-1-carboxylate
To a stirred solution of tert-butyl piperazine-1-carboxylate (32.8 g, 176 mmol) in THF (400 mL) were added TEA (44.5 mL, 439 mmol) and 1-bromo-4-(bromomethyl)benzene (40 g, 160 mmol) at 0 ^oC under nitrogen atmosphere. The resulting mixture was stirred for 2 h at room temperature and concentrated under reduced pressure. The residue was dissolved into DCM (100 mL) and washed with water (400 mL). The aqueous layer was extracted with DCM (2 x 200 mL). The combined organic layers was dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl 4-[(4-bromophenyl)methyl]piperazine-1- carboxylate (48 g, 84%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆) d 7.53-7.41 (m, 2H), 7.30-7.15 (m, 2H), 3.45 (s, 2H), 3.33-3.22 (m, 4H), 2.36-2.09 (m, 4H), 1.35 (s, 9H). LC/MS (ESI, m/z): [(M + 1)]⁺ = 355.00, 357.00

References:

KYMERA THERAPEUTICS, INC.;JI, Nan;MAINOLFI, Nello;WEISS, Matthew WO2020/10210, 2020, A1 Location in patent:Paragraph 00681