Benzyl Bromide → 1-(Benzyloxy)-7-bromoisoquinoline

HRID 1027281Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[OH:12])=[CH:4][CH:3]=1.[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:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:11]=2)[CH:6]=[CH:7][N:8]=1)[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-bottom flask containing 7-bromoisoquinolin-1-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 aqueous layer was extracted with DCM (2×), and the combined organics 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 (640 mg, 2.037 mmol, 91% yield). M+1=316.0. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.62 (d, J=2.01 Hz, 1H), 7.73 (dd, J=2.13, 8.41 Hz, 1H), 7.39 (d, J=8.28 Hz, 1H), 7.28-7.36 (m, 5H), 7.11 (d, J=7.53 Hz, 1H), 6.46 (d, J=7.28 Hz, 1H), 5.23 (s, 2H).

Workup

customto give a brown solution
temperatureAfter cooling to RT
concentrationthe reaction mixture was concentrated in vacuo
extractionThe aqueous layer was extracted with DCM (2×)
washthe combined organics 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-11917aeab6a949c9baa47522251f9377
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729263B2

Reaction notes

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