Hydrochloric Acid → HCID 59323143, compound

HRID 2390042Notes

Reaction equation

HRID 2390042 reaction equation
[C:1]([CH:9]1[CH2:18][C:17]2[C:12](=[CH:13][C:14]([F:19])=[CH:15][CH:16]=2)[CH2:11][N:10]1[C:20](OC)=O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[OH-].[Na+].Cl.C(OCC)(=O)C.[C:34]([N:41]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)CCO)(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)C.C1(C)C=CC=CC=1.[Pd].C(O)(=O)C.O>[CH2:45]([NH:41][CH2:34][CH2:20][N:10]1[CH:9]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:18][C:17]2[C:12](=[CH:13][C:14]([F:19])=[CH:15][CH:16]=2)[CH2:11]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10753247Tert-butyl N-benzyl-N-(2-hydroxyethyl)carbamateHCID 21866389Hydrogen chloride-ethyl acetate2×HCID 59323387HCID 59323387, compound

Product 1

HCID 59323143HCID 59323143, compoundYield 41%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 12 mg of 3-benzoyl-7-fluoro-2-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline in 2 mL of a 6 N aqueous hydrochloric acid solution was reacted under reflux for 16 hours. Under ice-cooling, the reaction liquid was diluted by addition of water, alkalized with 5 N sodium hydroxide, and extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow oily substance. 10 mg of the obtained yellow oily substance and 3 mg of 10% Pd-C were dissolved in 2 mL of ethanol and 0.2 mL of a 4N hydrochloric acid/ethyl acetate solution, followed by stirring at room temperature for 48 hours under a hydrogen atmosphere. The reaction liquid was filtered through Celite, and the filtrate was concentrated under reduced pressure to obtain 8 mg of a yellow oily substance. To a solution of 8 mg of the yellow oily substance and 9 mg of N-Boc-2-benzylaminoethanol in 1 mL of toluene were sequentially added 9 mg of sodium triacetoxyborohydride and 5 mg of acetic acid, followed by stirring at room temperature for 2 hours. It was alkalized by addition of an aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation to obtain 10 mg of a yellow oily substance. To this yellow oily substance was added 2 mL of 4N hydrochloric acid/ethyl acetate, followed by stirring at room temperature for 30 minutes. The organic layer was washed with an aqueous sodium bicarbonate solution and then with brine, and then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation. The residue obtained was purified using silica gel chromatography (chloroform: methanol=10:1) to obtain 2 mg (yield 41%) of a title compound as a yellow oily substance.

Workup

  1. temperatureunder reflux for 16 hours
  2. temperatureUnder ice-cooling
  3. customthe reaction liquid
  4. extractionextracted with chloroform
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto obtain a yellow oily substance
  9. customThe reaction liquid
  10. filtrationwas filtered through Celite
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customto obtain 8 mg of a yellow oily substance
  13. stirringby stirring at room temperature for 2 hours
  14. extractionfollowed by extraction with ethyl acetate
  15. washThe organic layer was washed with brine
  16. dry with materialdried over anhydrous sodium sulfate
  17. customthe solvent was removed by evaporation
  18. customto obtain 10 mg of a yellow oily substance
  19. stirringby stirring at room temperature for 30 minutes
  20. washThe organic layer was washed with an aqueous sodium bicarbonate solution
  21. dry with materialwith brine, and then dried over anhydrous sodium sulfate
  22. customthe solvent was removed by evaporation
  23. customThe residue obtained
  24. customwas purified

Sources & evidence

ORD record
ord-97f5ec25570f44d78326b626c9712fc9
Source dataset
uspto-grants-2012_09
Patent number
US08273766B2

Reaction notes

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