2-Chloro-N,N-dimethylethylamine → (S)-1-(3-((2-(Dimethylamino)ethoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone

Temperature

0 °C

To 2-chloro-N,N-dimethylethanamine (63 mg, 0.59 mmol) in DMF (1.0 mL) was added NaH (156 mg, 3.90 mmol, 60% suspension in mineral oil) at 0° C. After stirring for 20 min at 0° C., (S)-1-(3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (40 mg, 0.20 mmol) was added, and the resulting suspension was stirred at room temperature for 10 min. TBAI (7 mg, 0.019 mmol) was then added, and the reaction mixture was heated at 70° C. for 1.5 h. The mixture was then poured into sat. aq. NH4Cl solution and EtOAc. The layers were separated, and the organic layer was washed with sat. aq. NH4Cl solution. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. aq. NaCl solution and dried over Na2SO4. Filtration and concentration in vacuo provided a crude oil which was triturated with hexanes (3×) to give the title compound (29 mg, 54%) as a pale yellow oil. MS(ESI+) m/z 206.1 (M+H)+.

1. stirringthe resulting suspension was stirred at room temperature for 10 min
2. temperaturethe reaction mixture was heated at 70° C. for 1.5 h
3. customThe layers were separated
4. washthe organic layer was washed with sat. aq. NH4Cl solution
5. extractionThe aqueous layer was extracted with EtOAc (3×)
6. washthe combined organics were washed with sat. aq. NaCl solution
7. dry with materialdried over Na2SO4
8. filtrationFiltration and concentration in vacuo
9. customprovided a crude oil which
10. customwas triturated with hexanes (3×)

ORD record

ord-9ea0f0328a6b4a6f83a53babaacab1e0

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346795B2