Sodium Hydroxide → 3-[(1S)-2-tert-Butoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a 3-necked round-bottomed flask (100 ml with condenser, septum thermometer and magnetic follower) was charged sodium hydride (32.96 mmol, 1.32 g). The flask was placed under an inert atmosphere and dry NMP (80 ml) was charged. To the resulting suspension was charged (S)-1-tert-butoxy-2-propanol (30.21 mmol; 3.99 g; added in 0.2 ml aliquots with temperature control to control H2 evolution). Once gas evolution had ceased 3-fluoro-5-(4-methanesulfonyl-phenoxy)benzonitrile (see Example 1, 27.46 mmol, 8.0 g) was added in one portion. The reaction mixture was heated to 70° C. for 3 hours. The reaction was cooled to room temperature and toluene (240 ml) was added followed by water (240 ml). The contents were stirred at room temperature for 30 minutes and then transferred to a separating funnel. The two layers were separated and the aqueous layer was further extracted with toluene (240 ml). The organic extracts were combined and washed once with sodium hydroxide (160 mmol, 160 ml) and then with water (4×160 ml). The toluene was removed in vacuo to leave an oil that slowly solidified (9.20 g; 83.02% yield).

Provenance & Evidence