4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride in diethyl ether;tert-butyl methyl ether

Steps:

1
(IS*,4R*) formamide (1.0 g) was dissolved in THF (7 niL), and added BH₃ THF (IM, 9.3 mL, 3 eq. The reaction mixture was heated to 75-80°C for 3 h and stirred at rt overnight. The reaction mixture was quenched with MeOH (20 mL). The mixture was concentrated to give a residue, which was dissolved in 10% HCl (20 mL). The solution was heated to 80-90⁰C for 9 h, and basifed with potassium carbonate, and extracted with EtOAc (25 mL). The organic phase was separated and washed with water, brine, dried over Na₂SO₄. Concentrated to give the free base. It was converted to its HCl salt in TBME with HCl/Et2O to give the product (0.75g). ¹H MNR (CD₃OD) δ 1.86-1.96 (m, IH), 2.04-2.12 (m, IH), 2.18-2.28 (m, IH), 2.30-2.42 (m, IH), 2.78 (s, 3H), 4.34 (m, IH), 4.60 (m, IH), 6.93-7.00 (m, 2H), 7.15 (s, IH), 7.34-7.44 (m, 3H), 7.57-7.59 (d, J = 7.2 Hz, IH). Mass Spec. M⁺SOS.

References:

SEPRACOR INC. WO2007/6003, 2007, A2 Location in patent:Page/Page column 20; 23