Potassium Carbonate → tert-Butyl 4-(3-oxo-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-1-carboxylate

HRID 132209

Reaction equation

HRID 132209 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][C:16]([O:18]C)=O.[NH2:20][CH:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1>C(#N)C>[O:18]=[C:16]1[CH2:15][C:10]2[C:9](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][N:20]1[CH:21]1[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12682914-Amino-1-Boc-piperidineHCID 9855748Methyl 2-[2-(chloromethyl)phenyl]acetate

Product 1

HCID 59731897tert-Butyl 4-(3-oxo-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium carbonate (1.4 g, 10 mmol) was added to a solution of methyl 2-(2-(chloromethyl)phenyl)acetate (940 mg, 4.7 mmol) in acetonitrile (20 mL). 4-Amino-N-Boc-piperidine (1.13 g, 5.6 mmol) was added to the mixture. Reaction was heated at reflux for 1 hour. Mixture was cooled to room temperature and then filtered over celite. Filtrate was concentrated in vacuo. Residue was treated with toluene (29 mL). Acetic acid (1.5 ml) was added to the mixture. Reaction was heated at reflux for 2 hours. Mixture was concentrated in vacuo. Residue was treated with ethyl acetate (50 mL). Mixture was washed successively with aqueous sodium bicarbonate (2×30 mL), 1N hydrochloric acid (30 mL), and brine (20 mL). Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Silica gel chromatography gave the title compound as lightly colored oil in 40% yield. MS m/e (M+H)+=331.2.

Workup

  1. customReaction
  2. temperaturewas heated
  3. temperatureat reflux for 1 hour
  4. filtrationfiltered over celite
  5. concentrationFiltrate was concentrated in vacuo
  6. additionResidue was treated with toluene (29 mL)
  7. additionAcetic acid (1.5 ml) was added to the mixture
  8. customReaction
  9. temperaturewas heated
  10. temperatureat reflux for 2 hours
  11. concentrationMixture was concentrated in vacuo
  12. additionResidue was treated with ethyl acetate (50 mL)
  13. washMixture was washed successively with aqueous sodium bicarbonate (2×30 mL), 1N hydrochloric acid (30 mL), and brine (20 mL)
  14. dry with materialOrganic layer was dried (magnesium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7f3c353e3ba44efd995d03b8bbeced21
Source dataset
uspto-grants-2008_06
Patent number
US07384930B2

Linked notes

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