tert-butyl-4-bromoisoindoline-2-carboxylate synthesis

Yield:1035235-27-8 94%

Reaction Conditions:

with triethylamine in dichloromethane at 0 - 20; for 3 h;Inert atmosphere;

Steps:

Intermediate 4-bromoisoindoline-2-carboxylic acid benzyl ester
General procedure: 4-Bromoisoindoline hydrochloride (3.0 g, 13 mmol, 1 eq) was suspended in dry DCM (50 ml), and then TEA (5.4 ml, 39 mmol, 3 eq) was added. Reaction mixture was cooled to 0°C in an ice-bath, and then benzyl chloroformate (2.7 ml, 19 mmol, 1 .5 eq) dissolved in 10 ml DCM was added dropwise. Reaction was carried out under inert gas (nitrogen) atmosphere while stirring at room temperature for 3h. Reaction mixture was extracted thrice with saturated NaHCC solution, then once with water and with saturated NaCl solution. Organic phase was dried over anhydrous Na2S0₄, and then concentrated under reduced pressure to obtain white solid which was dried under vacuum. (0165) White solid, yield: 90% (3.8 g), Ci6Hi₄BrN0₂, MW 332.19, monoisotopic mass 331 .02, [M+H]⁺ 332.2, UPLC R_t = 8.12. ¹H NMR (300 MHz, CDCU) d (ppm) 4.73 (dd, J= 1 1 .6, 1 .4 Hz, 2H), 4.79-4.89 (m, 2H), 5.22 (d, J = 2.2 Hz, 2H), 7.09-7.50 (m, 7H).

References:

CELON PHARMA S.A.;UNIWERSYTET JAGIELLONSKI;INSTYTUT FARMAKOLOGII POLSKIEJ AKADEMII NAUK;KAMINSKI, Krzysztof;GRYCHOWSKA, Katarzyna;CANALE, Vittorio;BOJARSKI, Andrzej J.;SATALA, Grzegorz;LENDA, Tomasz;POPIK, Piotr;MATLOKA, Mikolaj;DUBIEL, Krzysztof;MOSZCZYNSKI-PETKOWSKI, Rafal;PIECZYKOLAN, Jerzy;WIECZOREK, Maciej;ZAJDEL, Pawel WO2019/97282, 2019, A1 Location in patent:Page/Page column 11; 12

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