Yield: 100%

Reaction Conditions:

in water at 50 - 55; for 4 h;Inert atmosphere;

Steps:

9.5 Step 5
Ester 4ε (695 g, 4.96 mol, 1.0 eq.) was added into 40 wt Me fc in water (3.5 L, 5 vol.) under a N₂ atmosphere. The suspension was heated to 50-55 °C for 3-4 h and gradually dissolved. The reaction was monitored by HPLC (HPLC showed 4c was consumed completely by HPLC). Water was removed by distillation at 65 °C. PhMe (3.5 L x 2) was added into the solid and the water was removed by distillation at 65 °C. 620 g of 4d was obtained as an off-white solid with 97 A% HPLC purity in quantity yield.

References:

EPIZYME, INC.;CAMPBELL, John Emmerson;DUNCAN, Kenneth William;MILLS, James Edward John;MUNCHHOF, Michael John WO2019/79540, 2019, A1 Location in patent:Paragraph 01615