Trifluoroacetic anhydride → 2,8-Dimethyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline

HRID 1526718Notes

Reaction equation

HRID 1526718 reaction equation
[CH3:1][N:2]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])[CH2:3][CH:4]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1)O.FC(F)(F)C(OC(=O)C(F)(F)F)=O>FC(F)(F)C(O)=O>[CH3:1][N:2]1[CH2:3][CH:4]([C:6]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:7]=2)[C:22]2[C:17](=[C:18]([CH3:23])[CH:19]=[CH:20][CH:21]=2)[CH2:16]1

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 689975302-[Methyl-(2-methyl-benzyl)-amino]-1-naphthalen-2-yl-ethanol

Product 1

HCID 689976452,8-Dimethyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolineYield 62%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

The product from Step A (1.25 g, 4.1 mmol) was dissolved in trifluoroacetic acid (TFA, 7.5 mL), then trifluoroacetic anhydride (TFAA, 7.5 mL) was added. After stirring for 24 h, the solvents were removed in vacuo, the residue was dissolved in MeOH, and the solvent was removed in vacuo. The residue was dissolved in aqueous NH4OH, then extracted twice with CH2Cl2. The extract was dried over Na2SO4, filtered, the solvent was removed in vacuo, and the residue was purified by column chromatography on silica gel (40 g) eluting with 5% to 30% EtOAc/hexanes with 1% Et3N to give 2,8-dimethyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline (0.73 g, 61%) as a clear, dark yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.66-7.88 (m, 4H), 7.38-7.48 (m, 2H), 7.26 (dd, J=8.3, 1.6 Hz, 1H), 6.93-7.04 (m, 2H), 6.74 (d, J=7.2 Hz, 1H), 4.45 (t, J=6.9 Hz, 1H), 3.75 (d, J=15.4 Hz, 1H), 3.51 (d, J=15.4 Hz, 1H), 3.06 (ddd, J=11.2, 5.6, 0.9 Hz, 1H), 2.67 (ddd, J=11.4, 8.5 Hz, 1H), 2.48 (s, 3H), 2.27 (s, 3H).

Workup

  1. customthe solvents were removed in vacuo
  2. dissolutionthe residue was dissolved in MeOH
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in aqueous NH4OH
  5. extractionextracted twice with CH2Cl2
  6. dry with materialThe extract was dried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customthe residue was purified by column chromatography on silica gel (40 g)
  10. washeluting with 5% to 30% EtOAc/hexanes with 1% Et3N

Sources & evidence

ORD record
ord-04bb6d17bb7b4ce9948ccf8833d6d0e4
Source dataset
uspto-grants-2015_07
Patent number
US09085531B2

Reaction notes

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