Isoquinoline → HCID 23518689, compound

HRID 1836315Notes

Reaction equation

[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.Cl[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[Li].BrC1C(F)=CC=CC=1F.[Li]CCCC>C1COCC1>[CH2:15]([O:14][C:12]([N:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]1[C:24]1[C:23]([F:22])=[CH:28][CH:27]=[CH:26][C:25]=1[F:29])=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of isoquinoline (645 mg; 5 mmol) in THF (20 mL) is treated with benzyl chloroformate (853 mg; 5 mmol) at 0° C., and the mixture stirred at 0° C. for 1 hour. 2,6-Difluorophenyllithium (prepared from 1-bromo-2,6-difluorobenzene (1.37 g; 7.1 mmol) and n-BuLi (2.5M in hexanes, 2.7 mL; 6.8 mmol at -78° C.) are added to this mixture and the resulting solution stirred at 0° C. for 1 hour and then at room temperature for 2 hours. The reaction is quenched with saturated NH4Cl solution, extracted with ether, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash chromatography over silica gel (elution with hexanes/ether 5;1) to give the product as a colorless oil (0.62 g) LC-MS [MH+] 378.2, RT=3.00 min.

Workup

additionare added to this mixture
stirringthe resulting solution stirred at 0° C. for 1 hour
waitat room temperature for 2 hours
customThe reaction is quenched with saturated NH4Cl solution
extractionextracted with ether
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated in vacuo
customThe residue is purified by flash chromatography over silica gel (elution with hexanes/ether 5;1)

Sources & evidence

ORD record: ord-13c770792961405ba4c57ab04f2f788a
Source dataset: uspto-grants-2004_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06777422B2

Reaction notes

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