反应详情

温度

2.5 °C

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.

1. customhigher than 15° C
2. additionAt the end of the addition a control by HPLC [COLUMN
3. customis kept to 25° C.
4. customtetrahydrofuran is evaporated under vacuum at 50° C
5. addition100 ml of ethyl acetate are added to the residue
6. customthe solvent is evaporated under vacuum at 50° C.
7. additionother 350 ml of ethyl acetate are added
8. customThe phases are separated
9. customthe organic phase is collected
10. extractionthe aqueous phase is extracted with 230 ml of ethyl acetate
11. customThe phases are separated
12. customthe organic phases are collected