86123-95-7

Boc-O-methyl-D-serine is used in preparation of acylamino acid heterocyclyl amides and deuterated derivatives for the treatment of BAF complex-related disorders.

The general procedure for the synthesis of (R)-2-tert-butoxycarbonylamino-3-methoxypropionic acid from BOC-L-serine and dimethyl sulfate was as follows: N-Boc-L-serine (22 g, 0.107 mol) was dissolved in anhydrous tetrahydrofuran (352 ml), the solution was cooled down to 0°C and the reaction mixture was stirred for 9 hours at 0-5°C. Upon completion of the reaction, the reaction was quenched by the addition of water (110 ml) and the pH was adjusted to 10-13 with 30% sodium hydroxide solution (3 ml). subsequently, the tetrahydrofuran/hexane mixture was removed by vacuum evaporation. The residue was washed with toluene (44 ml) and then acidified with 50% citric acid solution to pH < 3.5. The acidified aqueous phase was extracted with dichloromethane (2 x 91 ml, 1 x 66 ml) and the combined dichloromethane extracts were dried by azeotropic distillation. Eventually, evaporation of the solvent gave 23.7 g of product in 100% yield. The product was analyzed by HPLC showing 90.0% purity and 100% chiral purity.

[1] Patent: WO2006/37574, 2006, A1. Location in patent: Page/Page column 17
[2] Patent: WO2006/37574, 2006, A1. Location in patent: Page/Page column 17-18
[3] Patent: CN104030943, 2016, B. Location in patent: Paragraph 0103; 0104
[4] Patent: WO2012/51551, 2012, A1. Location in patent: Page/Page column 36-37
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