1-Methyl-3,4-dihydroisoquinoline → (R)-1-Methyl-1,2,3,4-tetrahydroisoquinoline

Temperature

-35 °C

To a cooled (−35° C.) solution of reducing agent 9 (526 mg, (0.78 mmol) in dichloromethane (3 mL) is added solution of 1-methyl-3,4-dihydroisoquinoline (32 mg, 0.22 mmol) in dichloromethane (3 mL) dropwise over 15 min. The mixture is allowed to warm to −10° C. over 1 h and then kept at 0° C. for 4 h. The solvent is removed in vacuo and the residue is dissolved in methanol (10 mL). After cooling to 0° C., Amberlyst 15 (1 g) is added and the mixture is shaken for 1 h at room temperature. The resin is filtered off and washed with dichloromethane and methanol, then solution of ammonia in methanol (2M, 3 mL) is added and the mixture is shaken overnight, then filtered. The filtrate is evaporated in vacuo to give (R)-1-Methyl-1,2,3,4-tetrahydroisoquinoline (26 mg, 82%, e.e.=74%, determined by chiral HPLC).

1. temperatureto warm to −10° C. over 1 h
2. customThe solvent is removed in vacuo
3. dissolutionthe residue is dissolved in methanol (10 mL)
4. temperatureAfter cooling to 0° C.
5. additionAmberlyst 15 (1 g) is added
6. filtrationThe resin is filtered off
7. washwashed with dichloromethane and methanol
8. additionsolution of ammonia in methanol (2M, 3 mL) is added
9. stirringthe mixture is shaken overnight
10. filtrationfiltered
11. customThe filtrate is evaporated in vacuo

ORD record

ord-6e2f0590732b411f9861dd419e4fd1f2

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07985753B2