Diisopropylamine → Citalopram

Participants

Reaction Conditions

Reaction Steps

n-BuLi (1.6 N in hexane, 320 mL) is added to diisopropylamine (55 g, 0.5 mole) dissolved in DME (150 mL) at −50° C. over a nitrogen atmosphere. 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (62 g, 0.26 mole) is dissolved in DME (500 mL) and added dropwise while the temperature is kept below −40° C. After addition (45 min), the dark red solution is stirred for an additional period of 20 min. 3-Dimethylpropylchloride (100 g, 0.82 mole) is added in one portion at −50° C. and the cooling is removed. After 60 min, the solution is warmed to 50° C. for 120 min. The reaction mixture is poured onto ice water (1 L) and extracted with toluene (2×500 mL). The organic phase is extracted with HCl (4 N, 500 mL). The acid solution is made alkaline (pH=10) with NaOH (10 N) and extracted with toluene (500 mL) which is washed with water (3×200 ml). The toluene phase is dried anhydrous Na2SO4 (50 g), treated with active carbon and the solvents are removed in vacuo. The title compound (64-71 g, 76-84%) is obtained as an oil.

Provenance & Evidence