Trifluoroacetic acid → HCID 71062294, compound

HRID 528965Notes

Reaction equation

HRID 528965 reaction equation
[C:1]1([NH:7]/[N:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].[N+]([C:24]([CH2:51][CH2:52][CH2:53][CH3:54])=[CH:25][C:26]1[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:28][C:27]=1[C:39]([N:41]1[CH2:50][CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42]1)=[O:40])([O-])=O.C(O)(C(F)(F)F)=O>C1COCC1>[C:33]([O:32][C:30]([C:29]1[CH:37]=[CH:38][C:26]([C:25]2[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:8][N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:24]=2[CH2:51][CH2:52][CH2:53][CH3:54])=[C:27]([C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[CH:28]=1)=[O:31])([CH3:34])([CH3:35])[CH3:36]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 13721206HCID 13721206, compoundHCID 23665647Potassium tert-butoxideHCID 71060717HCID 71060717, compound

Product 1

HCID 71062294HCID 71062294, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (E)-ethyl 2-(2-phenylhydrazono)acetate (31 mg, 0.16 mmol) in THF (1 mL) at −78° C. was added potassium tert-butoxide (0.161 mL, 0.161 mmol). After stirring at −78° C. for 15 min, a solution of tert-butyl 4-(2-nitrohex-1-enyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (75 mg, 0.161 mmol) in THF (1.0 mL) was added. After stirring at −78° C. for 15 min, TFA (0.024 mL, 0.323 mmol) was added and the reaction mixture became colorless. The reaction mixture was stirred at −78° C. for 2 h and was then allowed to warm to room temperature and stirred at room temperature for 30 min. The reaction mixture was quenched with sat. aq. sodium bicarbonate solution and then extracted with EtOAc. The organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting with 0-40% EtOAc/hexanes) to give the title compound (33 mg, 34%) as a colorless oil. 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.09 (dd, J=8, 2 Hz, 1H), 8.05-8.03 (m, 1H), 7.49-7.37 (m, 6H), 7.26-6.81 (m, 4H), 5.02-4.98 (m, 1H), 4.47-4.38 (m, 1H), 4.32-4.27 (m, 2H), 4.16-3.98 (m, 1H), 3.58-3.40 (m, 1H), 2.82-2.51 (m, 4H), 1.61 (s, 9H), 1.28 (t, J=8 Hz, 1.5H), 1.20 (t, J=8 Hz, 1.5H), 1.47-0.91 (m, 4H), 0.60-0.56 (m, 3H); MS(ESI+) m/z 608.3 (M+H)+.

Workup

  1. stirringAfter stirring at −78° C. for 15 min
  2. stirringThe reaction mixture was stirred at −78° C. for 2 h
  3. temperatureto warm to room temperature
  4. stirringstirred at room temperature for 30 min
  5. customThe reaction mixture was quenched with sat. aq. sodium bicarbonate solution
  6. extractionextracted with EtOAc
  7. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (Isco 40 g column eluting with 0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0cc9bd135e0044989179ab63f28dd285
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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