Lithium hydroxide, monohydrate → HCID 57781076, compound

HRID 1690760Notes

Reaction equation

HRID 1690760 reaction equation
[CH:1]1([N:4]2[C:13]([CH3:15])([CH3:14])[CH:12](C(O)=O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]2=[O:19])[CH2:3][CH2:2]1.C([O-])(=[O:22])C.[K+].C([O-])(=O)C.[Pb+4].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.O[Li].O>C(O)(=O)C.O.C1C=CC=CC=1>[CH:1]1([N:4]2[C:13]([CH3:15])([CH3:14])[CH:12]([OH:22])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]2=[O:19])[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 168937Lithium hydroxide, monohydrateHCID 517044Potassium AcetateHCID 57781096HCID 57781096, compoundHCID 178418268HCID 178418268, compound

Product 1

HCID 57781076HCID 57781076, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a solution of 2-cyclopropyl-3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-4-carboxylic acid (4.1 g, 15.8 mmol) in acetic acid (300 mL) is added benzene (150 mL), potassium acetate (10.9 g, 111 mmol), cupric acetate (0.145 g, 0.8 mmol) and lead (IV) acetate (12.7 g, 28.6 mmol). The green reaction mixture is heated to reflux for 2.5 h. The reaction mixture is then cooled to room temperature and quenched by the addition of ethylene glycol (ca. 6 mL). The resulting solution is the concentrated in vacuo to near dryness. The resulting dark green oil is dissolved in ethyl acetate (ca. 500 mL) and stirred vigorously while cautiously treating with saturated aqueous sodium bicarbonate (ca. 200 mL), followed by solid NaHCO3 until the aqueous layer reached a pH greater than 8. The layers are separated and the aqueous layer is extracted three times with ethyl acetate. The organic layer is dried with Na2SO4 filtered and concentrated. The resulting brown oil is then dissolved in THF (150 mL). Water (30 ml) and LiOH H2O (3.5 g, 83.4 mmol) are added. The reaction mixture is placed at 45° C. for 18 h, whereupon it is cooled to room temperature. The reaction is concentrated in vacuo to ca. ¾ of its original volume, diluted with methylene chloride and saturated aqueous NaHCO3. The layers are separated and the aqueous layer is extracted three times with ethyl acetate. The organic layers are combined, dried with Na2SO4, filtered and concentrated in vacuo to afford a brown oil. Purification by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:19 to 1:4) gave 2-cyclopropyl-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one as an off-white solid; MS (ESI) m/z 232.1 (M+H).

Workup

  1. temperatureThe green reaction mixture is heated
  2. temperatureto reflux for 2.5 h
  3. customquenched by the addition of ethylene glycol (ca. 6 mL)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting dark green oil is dissolved in ethyl acetate (ca. 500 mL)
  6. additionwhile cautiously treating with saturated aqueous sodium bicarbonate (ca. 200 mL)
  7. customThe layers are separated
  8. extractionthe aqueous layer is extracted three times with ethyl acetate
  9. dry with materialThe organic layer is dried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionThe resulting brown oil is then dissolved in THF (150 mL)
  13. temperatureis cooled to room temperature
  14. concentrationThe reaction is concentrated in vacuo to ca. ¾ of its original volume
  15. additiondiluted with methylene chloride and saturated aqueous NaHCO3
  16. customThe layers are separated
  17. extractionthe aqueous layer is extracted three times with ethyl acetate
  18. dry with materialdried with Na2SO4
  19. filtrationfiltered
  20. concentrationconcentrated in vacuo
  21. customto afford a brown oil
  22. customPurification by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:19 to 1:4)

Sources & evidence

ORD record
ord-bc7d5e279c04439780da643b4518e528
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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