Sodium Hydroxide → ST069377

Participants

Reaction Conditions

Reaction Steps

The organic phase (950 ml), containing a theoretical quantity of 150 g of 3-hydroxymethyl-4-(4-fluorobenzoyl)benzonitrile, referred to the starting 5-cyanophthalide, and about 14-16% of 3-hydroxymethyl-4-[bis(4-fluorophenyl)hydroxymethyl]benzonitrile, is cooled at 0-5° C., under nitrogen atmosphere. A solution of 23.3 g of NaBH4, 230 ml of water and 1 ml of 30% NaOH is added to the mixture dropwise, in 30 minutes and at a temperature not higher than 15° C. At the end of the addition a control by HPLC [COLUMN: Develosil C18 4.6×250 mm, 5μ; DETECTOR: UV 240 nm; FLOW: 1.5 ml/min; GRADIENT: A: aq. NH4H2PO4+H3PO4-pH=2.85/B: CH3CN/H2O=9/1 (v/v)] detects the disappearance of 3-hydroxymethyl-4-(4-fluorobenzoyl)benzonitrile. The temperature is kept to 25° C., the aqueous phase is eliminated and tetrahydrofuran is evaporated under vacuum at 50° C. 100 ml of ethyl acetate are added to the residue and the solvent is evaporated under vacuum at 50° C., then other 350 ml of ethyl acetate are added. The phases are separated, the organic phase is collected and the aqueous phase is extracted with 230 ml of ethyl acetate. The phases are separated, the aqueous phase is discarded and the organic phases are collected obtaining 720 ml of a solution in ethyl acetate containing 150 g of 3-hydroxymethyl-4-[(4-fluorophenyl)hydroxymethyl]benzonitrile and the same quantity of 3-hydroxymethyl-4-[bis(4-fluorophenyl)hydroxymethyl]benzonitrile contained into the starting solution.

Provenance & Evidence