Iodoethane → HCID 44255047, compound

HRID 2250138Notes

Reaction equation

HRID 2250138 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][CH2:7][CH2:6]2.[H-].[Na+].[CH2:16](I)[CH3:17]>C1COCC1>[CH2:16]([N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]1=[O:13])[CH3:17]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 106073926-methoxy-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 44255047HCID 44255047, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 6-methoxy-3,4-dihydro-2H-isoquinolin-1-one (0.30 g, 1.69 mmol) in THF (10 mL) is added sodium hydride (60% mineral oil suspension, 100 mg). The suspension is heated at reflux for 1 h, and cooled to room temperature. Ethyl iodide (1.4 mL, 17 mmol) is added, and the mixture is stirred at room temperature overnight. The mixture is partitioned between EtOAc and water. After the aqueous phase is extracted with EtOAc (2×), the combined organic phase is washed with brine and dried (MgSO4). After removal of the solvent, the residue is purified by flash chromatography (Biotage 40M SiO2, elute 45% EtOAc:hexane−50% EtOAc:hexane, linear gradient) to yield 2-ethyl-6-methoxy-3,4-dihydro-2H-isoquinolin-1-one as a colorless oil (0.275 g, 78%). The material is dissolved in CH2Cl2 (10 mL) and cooled to −78° C. To the cooled mixture is added a solution of boron tribromide (1 M, 4.7 mL, 4.7 mmol) in CH2Cl2. After 0.5 h, the temperature is warmed to 0° C. and stirred for 3 h. After the reaction is carefully quenched with ice, EtOAc and water is added, and the mixture is vigorously stirred overnight. The phases are separated, and the organic phase is extracted with EtOAc (2×). The combined organic phase is washed with brine and dried (MgSO4). The solvent is removed in vacuo, and the residue is purified by chromatography (Varian 10 g SiO2 cartridge, elute 60% EtOAc:hexane) to provide 2-ethyl-6-hydroxy-3,4-dihydro-2H-isoquinolin-1-one (0.209 g, 82%). MS (ES+) 192.0

Workup

  1. temperatureThe suspension is heated
  2. temperatureat reflux for 1 h
  3. customThe mixture is partitioned between EtOAc and water
  4. extractionAfter the aqueous phase is extracted with EtOAc (2×)
  5. washthe combined organic phase is washed with brine
  6. dry with materialdried (MgSO4)
  7. customAfter removal of the solvent
  8. customthe residue is purified by flash chromatography (Biotage 40M SiO2, elute 45% EtOAc:hexane−50% EtOAc:hexane, linear gradient)

Sources & evidence

ORD record
ord-7e380b1ee18948e8a427b4f0062de364
Source dataset
uspto-grants-2008_01
Patent number
US07314937B2

Reaction notes

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