1-(3-Hydroxyphenyl)-2-(methylamino)ethanone hydrochloride synthesis

Yield:94240-17-2 48%

Reaction Conditions:

Stage #1:2-bromo-1-(3-hydroxyphenyl)ethanone;methylamine in tetrahydrofuran at 5; for 2.5 h;ice-salt bath;
Stage #2: with hydrogenchloride in tetrahydrofuran;water at 0; for 0.5 h;

Steps:

2
The title compound was synthesized following a modified literature procedure (JP-A 63-192744). The whole procedure was performed under nitrogen atmosphere. A solution of methylamine (85 mL, 0.70 mol) in 250 mL tetrahydrofuran (THF) was cooled in an ice-salt bath. A solution of 2-bromo-3'-hydroxyacetophenone (42.5 g, 0.23 mol) in 750 mL of THF was added dropwise into the above solution within a period of 30 minutes. The temperature was kept below 5 °C, and after complete addition stirring was continued for 2 hours. At the beginning of addition, the solution became light yellow. The reaction was monitored by HPLC and TLC (eluent: CH₂Cl₂/Me0H, v:v = 10:1). The mixture was then concentrated under vacuum to remove excess of methylamine and some solvent (about 800 mL). The resulting solution (ca. 200 mL) was filtered in order to remove the CH₃NH₂HBr deposit, and then 30 mL of concentrated HCl was added dropwise within 30 minutes while cooling in an ice bath. Then, the mixture was evaporated under vacuum. 30 mL Ethanol and 15 mL methanol were added to the dark brown residue and the mixture was refluxed for 30 to 60 minutes. After cooling to room temperature, the mixture was filtered. The precipitate was washed with 30 mL absolute ethanol and dried under vacuum to get 19.2 g (48%) pale yellow solid. ¹H NMR (400 MHz, DMSO-J₆): δ 2.60 (s, 3H), 4.69 (s, 2H), 7.13-7.16 (d, J= 7.6 Hz, IH), 7.32-7 '.47 (m, 2H), 9.15 (s, 2H), 10.11 (s, IH) ¹³C NMR (100 MHz, DMSO-^₆): 5 32.6, 53.6, 114.1, 118.9, 121.8, 130.1, 134.9, 158.0, 192.3; MS: m/z 166 [M+H]⁺

References:

LONZA AG WO2008/77560, 2008, A1 Location in patent:Page/Page column 9-10

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