Trifluoroacetic acid → (S)-Methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

HRID 339231Notes

Reaction equation

HRID 339231 reaction equation
[C@H:1]1([NH:11][C:12]([C@@H:14]2[CH2:23][C:22]3[C:17](=[CH:18][C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:21]=3)[CH2:16][N:15]2C(OC(C)(C)C)=O)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C@H:1]1([NH:11][C:12]([C@@H:14]2[CH2:23][C:22]3[C:17](=[CH:18][C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:21]=3)[CH2:16][NH:15]2)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86705864(S)-2-tert-Butyl 7-methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylate

Product 1

HCID 86705866(S)-Methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-tert-butyl 7-methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylate (1.06 g, 2.28 mmol) in CH2Cl2 (22.8 mL) was added TFA (5.7 mL). The resulting reaction mixture was stirred at room temperature for 1 h and then quenched with sat. aq. NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×), and the combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was then lyophilized from MeCN/H2O overnight to give the title compound (0.79 g, 2.18 mmol, 96%) as a light yellow solid. 1H NMR (DMSO-d6) δ 8.39 (d, J=8.6 Hz, 1H), 7.85-7.67 (m, 2H), 7.34 (d, J=7.9 Hz, 1H), 7.24-7.02 (m, 4H), 5.12-4.93 (m, 1H), 4.23-3.97 (m, 2H), 3.86 (s, 3H), 3.73 (dd, J=10.0, 4.7 Hz, 1H), 3.33 (br s, 1H), 3.18-3.05 (m, 1H), 3.03-2.88 (m, 1H), 2.86-2.63 (m, 2H), 2.02-1.83 (m, 2H), 1.81-1.64 (m, 2H); MS (ESI+) m/z 365.1 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customquenched with sat. aq. NaHCO3 solution
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customwas then lyophilized from MeCN/H2O overnight

Sources & evidence

ORD record
ord-321373f19b0940e1b5830032a3eaab8d
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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