Dimethyl Sulfoxide → 3-[5'-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-2'-oxospiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]-2,2-dimethylpropanenitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of potassium t-butoxide (3.58 g, 31.9 mmol, 1.2 eq) in anhyd DMSO (72 mL) was added 5′-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)spiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (12.20 g, 26.6 mmol ) all at one time under a dry N2 atmosphere. After stirring 20 minutes, 3-chloro-2,2-dimethylpropionitrile (9.38 g, 79.8 mmol, 3 eq) was added drop-wise and the reaction was heated at 132° C. for 21 hr. After cooling in an ice bath, the reaction mixture was poured into H2O and extracted with Et2O. The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude product was purified on Biotage KP silica gel using a step gradient of CH2Cl2/CH3OH/NH4OH (99.25/0.5/0.25 to 96/2/1) to give the title compound as a yellow solid (9.48 g, 66% yield). NMR (400 MHz, DMSO-d6): consistent.

Provenance & Evidence