Potassium Carbonate → HCID 59536424, compound

HRID 445271Notes

Reaction equation

HRID 445271 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.C([O:33][C:34]([C:37](Cl)=[O:38])([CH3:36])[CH3:35])(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CO.O>[OH:33][C:34]([CH3:36])([CH3:35])[C:37]([N:10]1[CH2:11][CH2:12][C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=1)=[O:38]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 1234962-Acetoxyisobutyroyl chloride2×HCID 166406961-(4-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 59536424HCID 59536424, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (240 mg, 0.87 mmol, example 9 (step 3) and DIEA (151 μL, 0.87 mmol) in DCM (3 mL) was added 1-chlorocarbonyl-1-methylethyl acetate (125 μL, 0.87 mmol) slowly. After addition, the mixture was stirred at RT for 16 h. Then, an additional amount of 1-chlorocarbonyl-1-methylethyl acetate (60 μL) was added and the mixture was stirred at RT for 16 h. Then, H2O (2 mL) was added and the mixture was stirred at RT for 10 min. The organic layer was collected and the aqueous layer was extracted with EtOAc (2×3 mL). The combined organic extracts were then dried over MgSO4 and concentrated to give a crude intermediate. Then, the crude intermediate was dissolved in MeOH (10 mL), and then potassium carbonate (239 mg, 1.7 mmol) was added. The resulting mixture was then stirred at RT for 16 h. Then, the mixture was filtered and the solid was washed with DCM (2×5 mL). The combined filtrates were concentrated and the residue was purified by silica gel flash column chromatography (0%-400% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 364 (M+H).

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at RT for 16 h
  3. stirringthe mixture was stirred at RT for 10 min
  4. customThe organic layer was collected
  5. extractionthe aqueous layer was extracted with EtOAc (2×3 mL)
  6. dry with materialThe combined organic extracts were then dried over MgSO4
  7. concentrationconcentrated
  8. customto give a crude intermediate
  9. stirringThe resulting mixture was then stirred at RT for 16 h
  10. filtrationThen, the mixture was filtered
  11. washthe solid was washed with DCM (2×5 mL)
  12. concentrationThe combined filtrates were concentrated
  13. customthe residue was purified by silica gel flash column chromatography (0%-400% EtOAc/hexane)

Sources & evidence

ORD record
ord-b87ed91cd07b45b5bb9d89c11414b5b1
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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