Hydrochloric Acid → HCID 14097076, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 6 g (0.017 m) of N-(2,6-dichlorophenyl)-beta[(2,2-dimethylpropoxy)methyl]-1-pyrrolidineethanamine (the compound of Example 4b.), 4.2 g (0.042 m) of triethylamine, 3.28 g (0.018 m) of 4-picolinoylchloride in 100 ml of dry toluene was stirred at gentle reflux for 2.5 hrs then for 18 hrs at 25° C. Ether (50 ml), then ice and water were added followed by 3N NaOH. The aqueous layer was separated and extracted twice with EtOAc. The combined organic solution was washed with water then brine, dried (Na2SO4 and charcoal) and evaporated to yield a dark oil 7.4 g. This sample was combined with 5.3 g from another run and dissolved in 25 ml of CH2Cl2 and this solution was applied to a silica flash column (2"×71/4") containing 360 ml of silica gel and eluted with acetone:hexane 1:4. A 200 ml second fraction yielded 6 g of pure oily N-(2,6-dichlorophenyl)-N-[3-(2-methylpropoxy)-2-(pyrrolidinyl)propyl]-4-pyridinecarboxamide. A 4 g (0.0086 m) sample of the above 4-pyridinecarboxamide in 20 ml of THF was cooled in an ice bath and 26 ml of 1M (0.026 m) BH3.THF in THF was added over 15 mins. The reaction was stirred for 3 hrs at 25° C. and one hr at reflux. Reaction was cooled to 10° C. and an additional 10 ml of 1M BH3.THF was added. Reaction stirred at reflux for an additional 6 hrs and cooled. After addition of ice, 2 ml of methanol and 3 ml of 3N HCl was added and the solution stirred for 30 min. After making basic with 50% then 3N NaOH, the solution was extracted three times with CH2Cl2 ; extracted aqueous three times with EtOAc and combined all organic extracts (dried Na2SO4) and evaporated solvents off the give 3.35 of oil. Added ether to warm isopropanolic-ethereal HCl solution of the 3.35 g of oil. After cooling 3.1 g of crystalline HCl salt was collected. Recrystallizations from acetonitrile-ether then acetonitrile gave white plates (1.3 g) of title compound m.p. 227° C. (softens), melt 230°-23° C. (dec.)

Provenance & Evidence