Lithium hydroxide, monohydrate → HCID 10655326, compound

HRID 1690763Notes

Reaction equation

HRID 1690763 reaction equation
[CH3:1][C:2]1([CH3:16])[CH:11](C(O)=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:15])[NH:3]1.C([O-])(=[O:19])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.C1C=CC=CC=1.O>[OH:19][CH:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:15])[NH:3][C:2]1([CH3:16])[CH3:1]

Participants

8

Reactant 4

HCID 168937Lithium hydroxide, monohydrateHCID 517044Potassium AcetateHCID 57781109952494-13-2HCID 178418268HCID 178418268, compound2×

Product 1

HCID 10655326HCID 10655326, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a solution of 3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-4-carboxylic acid (5.0 g, 22.8 mmol) in acetic acid (450 mL) and benzene (160 mL) is added successively, potassium acetate (15.7 g, 160 mmol), cupric acetate (210 mg, 1.14 mmol), and lead (IV) acetate (18.2 g, 41.1 mmol). The green solution is heated to reflux for 4 h, at which time additional lead (IV) acetate (2.0 g 4.5 mmol) is added. After a total of 5 h at reflux the reaction is cooled to room temperature and quenched by the addition of ethylene glycol (ca. 5 mL). The reaction is concentrated in vacuo to near dryness. The resulting dark green oil is dissolved in ethyl acetate and stirred vigorously while cautiously treating with saturated aqueous sodium bicarbonate followed by solid NaHCO3 until the aqueous layer reached a pH greater than 8. The layers are separated and the aqueous layer is extracted 3 times with ethyl acetate. The organic layer is dried with Na2SO4 filtered and concentrated. The resulting brown oil is then dissolved in THF (200 mL). Water (40 ml) and LiOH.H2O (5.0 g, 118.6 mmol) are added. The reaction mixture is heated to 45° C. and stirred for 18 h, at which time 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 3 times with ethyl acetate. The organic layers are combined, dried with Na2SO4, filtered and concentrated in vacuo to afford a brown oil, which is pre-adsorbed on silica gel for further purification. Purification by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 23:2) furnished 4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one as an off-white foam; MS (ESI) m/z 192.1 (M+H).

Workup

  1. temperatureThe green solution is heated
  2. additionis added
  3. temperatureAfter a total of 5 h at reflux the reaction
  4. customquenched by the addition of ethylene glycol (ca. 5 mL)
  5. concentrationThe reaction is concentrated in vacuo
  6. dissolutionThe resulting dark green oil is dissolved in ethyl acetate
  7. additionwhile cautiously treating with saturated aqueous sodium bicarbonate
  8. customThe layers are separated
  9. extractionthe aqueous layer is extracted 3 times with ethyl acetate
  10. dry with materialThe organic layer is dried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe resulting brown oil is then dissolved in THF (200 mL)
  14. temperatureThe reaction mixture is heated to 45° C.
  15. stirringstirred for 18 h, at which time it
  16. temperatureis cooled to room temperature
  17. concentrationThe reaction is concentrated in vacuo to ca. ¾ of its original volume
  18. additiondiluted with methylene chloride and saturated aqueous NaHCO3
  19. customThe layers are separated
  20. extractionthe aqueous layer is extracted 3 times with ethyl acetate
  21. dry with materialdried with Na2SO4
  22. filtrationfiltered
  23. concentrationconcentrated in vacuo
  24. customto afford a brown oil, which
  25. customis pre-adsorbed on silica gel for further purification
  26. customPurification by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 23:2)

Sources & evidence

ORD record
ord-0ef78e6d8d1f469c970b787255968e98
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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