Ethylene Oxide → 4-[7-(2-Hydroxyethyl)-3-isoquinolinyl]benzonitrile

HRID 2390407Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[Li]CCCC.[CH2:25]1[O:27][CH2:26]1>C1COCC1>[OH:27][CH2:26][CH2:25][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -60 °C

Procedure

The product from Example 74A (4 mmol) is dissolved in 20 mL THF and is cooled to −60° C. under nitrogen. n-BuLi (4.4 mmol) is added dropwise, and the mixture is stirred at −60° C. for additional 30 minutes. A solution of ethylene oxide (20 mmol) in 10 ml THF is added and the mixture is allowed to warm to 10° C. and is stirred to complete the reaction. The mixture is cooled back down to 0° C. and is slowly quenched with 2N HCl to pH=3. The solvent is removed under vacuum and the residue is dissolved in 20 mL methylene chloride, is washed with water, and is concentrated under reduced pressure. The residue is chromatographed on silica gel (5:95 MeOH:CHCl3) to provide the title compound.

Workup

temperatureto warm to 10° C.
stirringis stirred
customthe reaction
temperatureThe mixture is cooled back down to 0° C.
customis slowly quenched with 2N HCl to pH=3
customThe solvent is removed under vacuum
dissolutionthe residue is dissolved in 20 mL methylene chloride
washis washed with water
concentrationis concentrated under reduced pressure
customThe residue is chromatographed on silica gel (5:95 MeOH:CHCl3)

Sources & evidence

ORD record: ord-3633c5982619465dbe462b6226a7e6bb
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273767B2

Reaction notes

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