Ethyl Acetate → Tert-butyl 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 2301123Notes

Reaction equation

HRID 2301123 reaction equation
Br.[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[CH:9]([CH3:14])[NH:8][CH2:7][CH2:6]2.C(=O)(O)[O-].[Na+].[C:20](=O)([OH:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].C(OCC)(=O)C>O.O1CCOCC1>[C:22]([O:21][C:20]([N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][C:12]([OH:13])=[C:3]([OH:2])[CH:4]=2)[CH:9]1[CH3:14])=[O:26])([CH3:25])([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 27337301-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrobromideHCID 3015642Mono-tert-butyl carbonate

Product 1

HCID 18377401Tert-butyl 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 99.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

6,7-Dihydroxy-1-methyl-1,2,3,4-tetrahydro-isoquinoline monohydrobromide (510 mg, 2.9 mol) was dissolved in water (5 ml) and dioxane (5 ml), and the solution was mixed with sodium bicarbonate (410 mg, 4.9 mmol) and t-butyl bicarbonate (470 mg, 2.2 mmol) and stirred at room temperature for 2.5 hours. Ethyl acetate was added to the reaction solution, and the organic layer was washed with dilute hydrochloric acid and saturated brine and then dried with anhydrous magnesium sulfate. The solvent was removed by evaporation from the organic layer under a reduced pressure and the thus obtained material was dried under a reduced pressure to obtain crude 2-t-butoxycarbonyl-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydro-isoquinoline (610 mg). Crude 2-t-butoxycarbonyl-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydro-isoquinoline (610 mg) was dissolved in anhydrous N,N-dimethylformamide (6 ml), and the solution was mixed with sodium hydride (60%, 170 mg, 4.1 mmol) and stirred at room temperature for 45 minutes. The reaction solution was mixed with methyl iodide (580 mg, 4.1 mmol) and again stirred for 1 hour. The reaction solution was mixed with ethyl acetate, washed with water and saturated brined and dried with anhydrous magnesium sulfate. The solvent was removed by evaporation from the organic layer under a reduced pressure, and the thus obtained material was separated and purified by a silica gel column chromatography to obtain 190 mg (0. 62 mmol, 32% in yield) of the title compound.

Workup

  1. washthe organic layer was washed with dilute hydrochloric acid and saturated brine
  2. dry with materialdried with anhydrous magnesium sulfate
  3. customThe solvent was removed by evaporation from the organic layer under a reduced pressure
  4. customthe thus obtained material was dried under a reduced pressure

Sources & evidence

ORD record
ord-f1f751a5a971447ca854e2d799e7f1bf
Source dataset
uspto-grants-2002_12
Patent number
US06498251B1

Reaction notes

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