Water → benzyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1585238Notes

Reaction equation

HRID 1585238 reaction equation
Br.[CH2:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[CH2:5][CH2:4][NH:3]1.O.Cl[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[CH2:18]([O:17][C:15]([N:3]1[CH2:4][CH2:5][C:6]2[C:11](=[CH:10][CH:9]=[C:8]([OH:12])[CH:7]=2)[CH2:2]1)=[O:16])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 133617991,2,3,4-Tetrahydroisoquinolin-6-ol--hydrogen bromide (1/1)

Product 1

HCID 54346727benzyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 114.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 8.00 g (49 mmol) of 6-Methoxy-1,2,3,4-tetrahydro-isoquinoline in 196 mL of 48% hydrobromic acid was refluxed for 3 h. The mixture was then concentrated and coevaporated several times with ethanol. The resulting slurry was filtered and dried under vacuum to give 7.43 g of 1,2,3,4-Tetrahydro-isoquinolin-6-ol hydrobromide as a solid. To 7.38 g of the crude hydrobromide dissolved in 117 mL each of dioxane and water was added 6.34 g (35.3 mmol) of benzyl chloroformate with ice bath cooling. A 1 M solution of potassium carbonate was slowly added until a pH of 10 was maintained. The mixture was stirred overnight at room temperature. Excess dioxane was removed by evaporation, and the resulting aqueous mixture was acidified with 1 N HCl and the product extracted with ethyl acetate. The organic portion was washed with water and brine, dried over Na2SO4 and concentrated to give 10.4 g of an oil which was crystallized from ether/hexane to give 7.05 g of 7D as a solid.

Workup

  1. temperaturecooling
  2. temperaturewas maintained
  3. customExcess dioxane was removed by evaporation
  4. extractionthe product extracted with ethyl acetate
  5. washThe organic portion was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f857508b68c34c36a1ae4bb2b627cec5
Source dataset
uspto-grants-1999_08
Patent number
US05936089

Reaction notes

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