Iodine → [2-(1-Methylethyl)-2,3-dihydro-1H-isoindol-5-yl]boronic acid

HRID 1805893Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([CH:11]([CH3:13])[CH3:12])[CH2:5]2.[Mg].II.[B:17](OC)([O:20]C)[O:18]C>O1CCCC1>[CH3:12][CH:11]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([B:17]([OH:20])[OH:18])[CH:3]=2)[CH2:7]1)[CH3:13]

Participants

Conditions

Temperature: 5 °C

Procedure

A solution of 5-bromo-2-(1-methylethyl)-2,3-dihydro-1H-isoindole (Intermediate 6, 20 g) in dry tetrahydrofuran (THF) (200 mL) was added to magnesium turnings (3.04 g). To this was added a crystal of iodine and the reaction mixture was heated at reflux for 4 hours. The reaction mixture was cooled to 5° C. and to this was added trimethyl borate (11.17 mL). After 1 hour the reaction was quenched with 2N hydrochloric acid (200 mL). The aqueous phase was extracted with ethyl acetate (3×200 mL), with each extraction was added triethylamine (50 mL). The combined organics were dried over magnesium sulphate and evaporated in vacuo to give a brown foam. This was triturated with TBME (300 mL) and the solid was collected by filtration to give the title compound (9.0 g) as an off-white solid.

Workup

temperaturethe reaction mixture was heated
temperatureat reflux for 4 hours
customAfter 1 hour the reaction was quenched with 2N hydrochloric acid (200 mL)
extractionThe aqueous phase was extracted with ethyl acetate (3×200 mL), with each extraction
additionwas added triethylamine (50 mL)
dry with materialThe combined organics were dried over magnesium sulphate
customevaporated in vacuo
customto give a brown foam
customThis was triturated with TBME (300 mL)
filtrationthe solid was collected by filtration

Sources & evidence

ORD record: ord-442097ce79184702b74b3e69cb7b0699
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354539B2

Reaction notes

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