Sodium Hydroxide → (1R,3S)-1-(4-chlorophenyl)-3-methyl-1,2,3,4-tetrahydroisoquinoline
Reaction equation
FC(F)(F)S(O)(=O)=O.[Cl:9][C:10]1[CH:26]=[CH:25][C:13]([CH:14]=[N:15][C@@H:16]([CH3:24])[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:12][CH:11]=1.[OH-].[Na+]>>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:14]2[C:19]3[C:18](=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][C@H:16]([CH3:24])[NH:15]2)=[CH:25][CH:26]=1Participants
4
Conditions
- Temperature
- 120 °C
Procedure
To a flask with trifluoromethanesulfonic acid (3.00 mL, 34 mmol) at 0° C. was added dropwise (S)—N-(4-chlorobenzylidene)-1-phenylpropan-2-amine (1.20 g, 1.61 mmol) and the reaction was heated to 120° C. and stirred 19 h under N2. The reaction was cooled, poured into ice water (20 mL), and basisified with 5 N NaOH (6 mL). The aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic layers were washed with saturated NaCl (20 mL), dried (MgSO4), and concentrated to give a yellow/brown oil. The residue was purified by ISCO (40 g SiO2, 0-100% EtOAc/hexane) to give (1R,3S)-1-(4-chlorophenyl)-3-methyl-1,2,3,4-tetrahydroisoquinoline as a light yellow oil.