Trifluoroacetic acid → (S)-7-Nitro-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HRID 339252Notes

Reaction equation

HRID 339252 reaction equation
[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][C@@H:9]([C:21](=[O:33])[NH:22][C@H:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:26][CH2:25][CH2:24]3)[N:10](C(OC(C)(C)C)=O)[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][C@@H:9]([C:21]([NH:22][C@H:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:26][CH2:25][CH2:24]3)=[O:33])[NH:10][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86705876(S)-tert-butyl 7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate2×

Product 1

HCID 86705890(S)-7-Nitro-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamideYield 97.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound C of Example 20, 4.45 g, 9.86 mmol) in CH2Cl2 (49 mL) was added TFA (11.4 mL, 148 mmol). The resulting solution was stirred at room temperature for 1 h and then quenched carefully with sat. NaHCO3 until bubbling ceased. The aqueous layer was extracted with CH2Cl2 (3×), and the combined organic extracts were washed with sat. NaHCO3, water and sat. NaCl. The extracts were dried over Na2SO4, filtered and concentrated in vacuo to give 3.38 g of the title compound as a pale yellow solid. 1H NMR (CDCl3, mixture of amide rotamers) δ 8.05 (d, J=6.6 Hz, 1H), 7.97-7.88 (m, 1H), 7.53-7.32 (m, 2H), 7.22-6.94 (m, 4H), 5.25-5.03 (m, 1H), 4.18-3.94 (m, 2H), 3.83-3.65 (m, 1H), 3.35 (dd, J=16.7, 5.1 Hz, 1H), 3.09 (dd, J=17.1, 9.1 Hz, 1H), 2.90-2.70 (m, 2H), 2.18-1.96 (m, 1H), 1.93-1.44 (m, 3H); MS (ESI+) m/z 352.2 (M+H)+.

Workup

  1. customquenched carefully with sat. NaHCO3
  2. customuntil bubbling
  3. extractionThe aqueous layer was extracted with CH2Cl2 (3×)
  4. washthe combined organic extracts were washed with sat. NaHCO3, water and sat. NaCl
  5. dry with materialThe extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7791cce339b54963bbccac7d5a45681a
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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