Pyridine → Triphosgene

Participants

Reaction Conditions

Reaction Steps

In a three-neck flask the solution of triphosgene (10.87 g, 36.63 mmol) in toluene (60 mL) is prepared at room temperature (23° C.), then the reactor is placed in an ice-water cooling bath. In a separate flask (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (20.0 g, 95.55 mmol, purity 99% (HPLC)) and pyridine (3.26 mL, 40.30 mmol) are placed in toluene (80 mL), while heating at 50-70° C. until the whole amount of solid is dissolved. After cooling down to room temperature, the clear toluene solution is transferred into a dropping funnel. The solution is added dropwise within ca. 10 min. to triphosgene in toluene solution. When the addition is complete, the cooling bath is removed and the reactor is submerged in an oil bath. Reaction mixture is heated at 70-80° C., in a mean time thick yellow solid slowly dissolves. Since reaction temperature reaches 50° C., heating and stirring is continued for 45 min., until disappearance of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline signal (TLC control in CH2Cl2—MeOH 95:5, v/v against substrate sample) is observed. After completion of the reaction the mixture is cooled down to room temperature (20-24° C.), filtered through celit to remove precipitated pyridinium hydrochloride. Celit layer is washed with toluene (20 mL). Toluene (145 mL) is removed under reduced pressure (0.1-0.15 mmHg) from the post-reaction mixture, while heating the condensing flask in a water bath at 60-65° C. The oily residue is dissolved in heptan (200 mL) at reflux and the hot solution is filtered through celit (20 g), washed with heptan before filtration. The celit layer is washed with hot heptan (2×50 mL) after filtration. The excess of solvent (170 mL) is removed under reduced pressure; the condensed solution to ca. ½ volume is left at 5° C. for 12 h. Crystalline, colorless solid is filtered off and washed with heptan (2×15 mL). (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinolinecarbonyl chloride is obtained in 23.3 g, 90% yield; purity (HPLC) 98.4%; T(onset)=62.7° C.

Provenance & Evidence