Sulfuric Acid → 5-Bromo-8-fluoroisoquinolin-3-ol

HRID 1926247Notes

Reaction equation

HRID 1926247 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([CH:16]=1)[CH2:7][NH:8][C:9](=[O:15])[CH:10](OC)OC.OS(O)(=O)=O.OS(O)(=O)=O.O=S(=O)=O.C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]2[C:16]=1[CH:10]=[C:9]([OH:15])[N:8]=[CH:7]2

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 24681Fuming sulfuric acidHCID 516892Sodium BicarbonateHCID 67520949N-(5-bromo-2-fluorobenzyl)-2,2-dimethoxyacetamide

Product 1

HCID 1785152975-Bromo-8-fluoroisoquinolin-3-ol

Conditions

Temperature
85 °C

Procedure

To N-(5-bromo-2-fluorobenzyl)-2,2-dimethoxyacetamide (12.0 g, 39 mmol) were added concentrated H2SO4 (21 mL) and oleum (30%, 25.0 mL, 394 mmol). The mixture was heated at 85° C. for 2 h. The reaction mixture was cooled to ambient temperature and poured slowly into a cold aqueous satd. solution of NaHCO3 in a beaker with efficient stirring (Note: frothing occurs). The solid that formed was filtered off, washed with water (50 mL), and dried in vacuo to give the title compound as yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ=7.03 (s, 1H), 7.11 (dd, J=7.2, 2.1 Hz, 1H), 7.98 (dd, J=7.2, 2.4 Hz, 1H), 9.15 (s, 1H). MS (ES+): m/z 242.11/244.13 [MH+]. HPLC: tR=2.63 min (ZQ2, polar—5 min).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. additionpoured slowly into a cold aqueous satd
  3. customThe solid that formed
  4. filtrationwas filtered off
  5. washwashed with water (50 mL)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-7cf78fdc1a604ee284c6cd2d9b23ba0d
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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