Benzyl Bromide → 3-(Benzyloxy)-6-bromoisoquinoline

HRID 1027279Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

To a 25 mL round-bottomed flask containing 6-bromoisoquinolin-3-ol (500 mg, 2.23 mmol) was added TEA (0.467 mL, 3.35 mmol) and benzyl bromide (0.319 mL, 2.68 mmol) in DMF (10 mL) to give a brown solution. The reaction was heated to 80° C. overnight. After cooling to RT, the reaction mixture was concentrated in vacuo, and taken up in DCM and water. The water was extracted with DCM (2×), and the combined organic fractions were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purify by flash column chromatography (10-30-50% EtOAc/Heptanes), providing the title compound (132 mg, 0.420 mmol, 19% yield). M+1=316.0. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.92 (s, 1H), 7.85 (d, J=1.25 Hz, 1H), 7.74 (d, J=8.78 Hz, 1H), 7.31-7.52 (m, 6H), 6.99 (s, 1H), 5.48 (s, 2H).

Workup

customto give a brown solution
temperatureAfter cooling to RT
concentrationthe reaction mixture was concentrated in vacuo
extractionThe water was extracted with DCM (2×)
washthe combined organic fractions were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purify by flash column chromatography (10-30-50% EtOAc/Heptanes)

Sources & evidence

ORD record: ord-5db55eb0dbf6489e8736e48f049df237
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729263B2

Reaction notes

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