Trifluoroacetic acid → (S)-3-(Azidomethyl)-1,2,3,4-tetrahydroisoquinoline

HRID 528857Notes

Reaction equation

HRID 528857 reaction equation
[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1C(OC(C)(C)C)=O)=[N+:2]=[N-:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][NH:6]1)=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 10869941(S)-tert-butyl 3-(azidomethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 86718892(S)-3-(Azidomethyl)-1,2,3,4-tetrahydroisoquinolineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 3-(azidomethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Page, D. et al., J. Med. Chem., 44:2387-2390 (2001)) (509 mg, 1.77 mmol) in CH2Cl2 (8.0 mL) was added TFA (2.7 mL, 35.3 mmol). The resulting reaction mixture was stirred at room temperature for 1 h and then concentrated in vacuo. The residue was dissolved in CH2Cl2 and washed with sat. aq. NaHCO3 solution (2×). The aqueous layer was extracted with CH2Cl2 (2×), and the combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to provide the title compound (302 mg, 91%) as a clear, colorless oil. 1H NMR (CDCl3) δ 7.17-7.13 (m, 2H), 7.12-7.08 (m, 1H), 7.07-7.02 (m, 1H), 4.14-4.05 (m, 2H), 3.55 (dd, J=12.2, 4.4 Hz, 1H), 3.45-3.39 (m, 1H), 3.16-3.09 (m, 1H), 2.82-2.75 (m, 1H), 2.70-2.60 (m, 1H), 2.02 (br s, 1H); MS(ESI+) m/z 189.1 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2
  4. washwashed with sat. aq. NaHCO3 solution (2×)
  5. extractionThe aqueous layer was extracted with CH2Cl2 (2×)
  6. dry with materialthe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1b2045da9c0345d9b5958f42d1024070
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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