Hydrochloric Acid → HCID 58928334, compound

Participants

Reaction Conditions

Reaction Steps

A CH2Cl2 solution of [(6R,9aS)-6-(4-methoxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-methanone obtained in step 5 (2.30 g, 5.14 mmoles) is treated with 15.4 mL of HCl (1 M in Et2O) and allowed to stand for 10 min. This solution is concentrated in vacuo and then dissolved in 70 mL anhydrous CH2Cl2. This solution is cooled to −70° C. (dry ice/isopropanol bath) under nitrogen and treated with BBr3 (1 M in DCM, 20.6 mL) dropwise via syringe over 20 mins. The mixture is stirred for 18 h while warming to ambient temperature. After this time, the mixture is cooled to 0° C., treated with 150 mL saturated NaHCO3 and stirred vigorously for 30 min. The phases are separated and the aqueous phase is extracted three times with CH2Cl2. The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo to afford [(6R,9aS)-6-(4-hydroxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-methanon as a light brown solid which is used without additional purification. LC/MS: 434 (M+1). 1H NMR (mixture of rotamers, 400 MHz, CDCl3): 8.74 (1H, d), 7.94 (1H, dd), 7.88 (1H, dd), 7.22 (1H, dd), 6.64 (1H, dd), 4.92 (1H, bs), 4.50 (1H, dd), 3.41-3.30 (2H, bm), 3.21 (1H, m), 3.03 (1H, m), 2.91-2.53 (3H, bm), 2.25-2.14 (6H, m), 1.92-1.58 (5H, bm), 1.20-1.32 (3H, bm).

Provenance & Evidence