Yield:1307231-21-5 14 g

Reaction Conditions:

with triethylamine in dichloromethane at 0 - 20;

Steps:

(S)-tert-butyl 4-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (IND INT-15)

(S)-tert-butyl 4-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (IND INT-15)
To crude (S)-4-bromo-2,3-dihydro-1H-inden-1-amine hydrochloride IND INT-13 (16.6 g, 66 mmol) in DCM (140 mL) at 0° C. was added triethylamine (14.8 g, 146 mmol) and di-tert-butyl dicarbonate (16.0 g, 73 mmol).
The reaction was stirred at room temperature overnight.
The reaction was diluted with DCM (50 mL) and washed with water and brine.
The organic layers were dried over MgSO₄ and the product purified by crystallization from 10% EA/hexanes to afford 14 g of (70%) (S)-tert-butyl 4-bromo-2,3-dihydro-1H-inden-1-ylcarbamate IND INT-15 as an off-white solid. LCMS-ESI (m/z) calculated for C₁₄H₁₈BrNO₂: 312.2. found 197.0 [M-NH₂Boc]⁺, t_R=3.94 min. ¹H NMR (400 MHz, CDCl₃) δ 7.38 (d, J=7.9 Hz, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.08 (t, J=7.7 Hz, 1H), 5.25 (dd, J=15.9, 7.9 Hz, 1H), 4.78 (d, J=7.6 Hz, 1H), 2.99 (ddd, J=16.5, 9.0, 3.4 Hz, 1H), 2.81 (dt, J=16.5, 8.2 Hz, 1H), 2.70-2.36 (m, 1H), 1.94-1.71 (m, 1H), 1.47 (d, J=5.2 Hz, 9H).
¹³C NMR (101 MHz, CDCl₃) δ 155.99, 146.13, 143.83, 131.35, 129.02, 123.41, 120.64, 80.10, 57.21, 33.71, 31.82, 28.86; Chiral HPLC: (S)-tert-butyl 4-bromo-2,3-dihydro-1H-inden-1-ylcarbamate was eluted using 2% IPA in hexanes: >99.9% ee, t_R=11.08 min.
(R)-tert-butyl 4-bromo-2,3-dihydro-1H-inden-1-ylcarbamate IND INT-16 was prepared in an analogous fashion from (R)-4-bromo-2,3-dihydro-1H-inden-1-amine hydrochloride IND INT-14: >99.9% ee t_R for (R)-enantiomer=9.98 min.

References:

US2015/299179,2015,A1 Location in patent:Paragraph 0299; 0300