4-Methoxynaphthalen-1-aMine hydrochloride synthesis

Yield:92599-05-8 90%

Reaction Conditions:

Stage #1: 1-methoxy-4-nitronaphthalenewith hydrazine hydrate in methanol; for 2 h;Reflux;
Stage #2: with hydrogenchloride in 1,4-dioxane;diethyl ether;

Steps:

Preparation of 4-methoxynaphthalen-1-aminium chloride (MC4197, 22)

1-Methoxy-4-nitronaphthalene (1 g, 4.9 mmol) was dissolved in 10 mL of methanol followed by addition of 80% hydrazine hydrate (1 mL). Raney nickel (0.3 mg) was carefully added before the mixture was refluxed. After completion of the reduction (2 hours), the catalyst was filtered out and methanol was removed under reduced pressure. The obtained crude 4-methoxynaphthalen-1-amine was converted to the corresponding hydrochloric salt (22) via treatment of the amine in dry diethyl ether with 4 N HCl in dioxane (12.5 mL). Yield: 90%. mp 249-250 . ¹H-NMR (400 MHz, DMSO) δ 4.0 (s, 3H, OCH₃), 6.94-6.96 (d, 1H, C₃-H naphthyl ring), 7.47-7.50 (d, 1H, C₂-H naphthyl ring), 7.55-7.60 (m, 1H, C₇-H naphthyl ring), 7.63-7.67 (m, H, C_6,-H naphthyl ring), 7.91-7.93 (d, 1H, C₈-H naphthyl ring), 8.16-8.18 (d, 1H, C₅-H naphthyl ring), 10.18 (sb, 3H, NH₂·HCl). ¹³C-NMR (100 MHz, DMSO) δ 55.74, 110.71, 117.93, 122.97, 123.59, 123.97, 126.94, 128.57, 129.72, 140.75, 151.37. HR-MS (ESI) calcd for C₁₁H₁₂NO [M+H]⁺ 174.0913, found 174.0915. Anal. (C₁₁H₁₂ClNO) Calcd. (%): C, 63.01; H, 5.77; Cl, 16.91; N, 6.68; O, 7.63. Found (%): C, 63.08; H, 5.78; Cl, 16.87; N, 6.66; O, 7.61.

References:

Wapenaar, Hannah;van den Bosch, Thea;Leus, Niek G.J.;van der Wouden, Petra E.;Eleftheriadis, Nikolaos;Hermans, Jos;Hailu, Gebremedhin Solomon;Rotili, Dante;Mai, Antonello;D?mling, Alexander;Bischoff, Rainer;Haisma, Hidde J.;Dekker, Frank J. [European Journal of Medicinal Chemistry,2017,vol. 136,p. 480 - 486] Location in patent:supporting information