Triethylamine → (4-Methoxy-benzyl)-(2-thiophen-3-yl-ethyl)-amine Hydrochloride

Temperature

0 °C

A solution of 2-(3-thienyl)ethanamine hydrochloride (1.0 g, 6.1 mmol), 4-methoxybenzaldehyde (0.74 mL, 6.1 mmol), and triethylamine (1.7 mL, 12.2 mmol) in ethanol (60 mL) was stirred at 25° C. for 5 h. The reaction mixture was cooled to 0° C. and sodium borohydride (289 mg, 7.6 mmol) was added portionwise over 30 min. The reaction mixture was warmed to 25° C. and stirred for 1 h. The reaction mixture was diluted with acetone (5 mL) dropwise and concentrated to a residue that was dissolved in CH2Cl2 (10 mL) and 1.0 N NaOH (10 mL). The aqueous layer was separated and extracted with CH2Cl2 (10 mL). The combined organic extracts were washed with brine (10 mL), dried with Na2SO4, filtered, and concentrated to give a crude oil which was purified using flash column chromatography (30% ethyl acetate/hexane →90% EtOAc/hexane). The fractions containing the amine were acidified with 2 N HCl in 1,4-dioxane to yield 4.11-A as a white solid (1.3 g, 78%). 1H NMR (500 MHz, CD3OD): δ 7.46–7.43 (m, 3H), 7.26–7.25 (m, 1H), 7.07–7.06 (m, 1H), 7.05–7.02 (m, 2H), 4.18 (s, 2H), 3.85 (s, 3H), 3.31–3.28 (m, 2H), 3.08 (dd, J=8.3, 7.8 Hz, 2H); LCMS found for C14H 18NOS (M+H)+: m/z=248.

1. temperatureThe reaction mixture was warmed to 25° C.
2. concentrationconcentrated to a residue that
3. dissolutionwas dissolved in CH2Cl2 (10 mL)
4. customThe aqueous layer was separated
5. extractionextracted with CH2Cl2 (10 mL)
6. washThe combined organic extracts were washed with brine (10 mL)
7. dry with materialdried with Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a crude oil which
11. customwas purified
12. additionThe fractions containing the amine

ORD record

ord-e9ce31802b6a46648f2d86b435f35930

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07141596B2