Ethylene Oxide → 7-(2-Hydroxy-ethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-Butyl Ester

HRID 564049Notes

Reaction equation

HRID 564049 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12](I)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.[Cl-].[Li+].[O:26]1[CH2:28][CH2:27]1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([CH2:28][CH2:27][OH:26])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6354Ethylene OxideHCID 433294Lithium ChlorideHCID 67006732Tert-butyl 7-iodo-3,4-dihydroisoquinoline-2(1h)-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 670071427-(2-Hydroxy-ethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To 1.80 g (5.00 mmol) 7-iodo-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (preparation 7b) in 5.0 mL THF at −20° C. is added 6.34 g (5.50 mmol) of a THF-solution of 14% isopropylmagnesium-chloride*lithiumchloride under argon. The mixture is warmed to 0° C. and stirred 1 h at 0° C. The reaction mixture is cooled to −60° C. and 0.88 g (20.0 mmol) oxirane in 2.0 mL THF is added. The cooling bath is removed and the reaction is warmed to RT. The reaction mixture is poured into 50 mL aqueous ammonium chloride solution and the aqueous phase is extracted with EtOAc. The combined organic phase is washed with water, dried over MgSO4. After filtration and evaporation of the solvent, the residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95).

Workup

  1. temperatureThe reaction mixture is cooled to −60° C.
  2. customThe cooling bath is removed
  3. temperaturethe reaction is warmed to RT
  4. additionThe reaction mixture is poured into 50 mL aqueous ammonium chloride solution
  5. extractionthe aqueous phase is extracted with EtOAc
  6. washThe combined organic phase is washed with water
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtration and evaporation of the solvent
  9. customthe residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95)

Sources & evidence

ORD record
ord-20df941e14084e86a172c8eec4d7b68a
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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