Sodium Hydroxide → (1R,3S)-1-(4-chlorophenyl)-3-methyl-1,2,3,4-tetrahydroisoquinoline

HRID 445320Notes

Reaction equation

HRID 445320 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]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 59536354(S)-N-(4-chlorobenzylidene)-1-phenylpropan-2-amine

Product 1

HCID 59536413(1R,3S)-1-(4-chlorophenyl)-3-methyl-1,2,3,4-tetrahydroisoquinoline

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.

Workup

  1. temperatureThe reaction was cooled
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  3. washThe combined organic layers were washed with saturated NaCl (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give a yellow/brown oil
  7. customThe residue was purified by ISCO (40 g SiO2, 0-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-168e531f127742d8b2fb19537bbe7931
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

Loading…