Hydrochloric Acid → 3-[7-(2-chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid

HRID 506989Notes

Reaction equation

HRID 506989 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C:13]3[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=3[CH3:22])[C:16]([OH:18])=[O:17])[C:9]2=[O:12])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][Cl:32].[OH-].[Na+].Cl>CN(C=O)C>[Cl:32][CH2:31][CH2:30][O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C:13]3[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=3[CH3:22])[C:16]([OH:18])=[O:17])[C:9]2=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 78491-Bromo-2-ChloroethaneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 670185873-(7-hydroxy-1-oxo-1H-isoquinolin-2-yl)-4-methylbenzoic acid

Product 1

HCID 670185953-[7-(2-chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzoic acid (5.9 g) was dissolved in DMF (120 ml). Potassium carbonate (27.6 g) and 1-bromo-2-chloroethane (9.99 ml) were added and heated at 50° C. for 18 hours. The reaction mixture was cooled to 40° C. and 2N NaOH (20 ml) was added and the mixture heated at 40° C. for 18 hours. The cooled reaction mixture was adjusted to pH 1 using concentrated hydrochloric acid to yield a brown oil. This oil was extracted with methylene chloride (×2), the organic solution was filtered through silicone treated filter paper (Whatman 1PS) and concentrated to yield 3-[7-(2-chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid as a brown oil (6.59 g); NMR Spectrum: (DMSOd6) 2.22 (s, 1H), 3.85 (m, 2H), 4.40 (m, 2H), 6.60 (m, 1H), 6.95 (m, 1H), 7.40 (m, 1H), 7.46 (m, 1H), 7.56 (m, 1H), 7.90 (m, 1H), 7.95 (m, 1H); Mass Spectrum: M+H+ 358.

Workup

  1. temperatureThe reaction mixture was cooled to 40° C.
  2. temperaturethe mixture heated at 40° C. for 18 hours
  3. customThe cooled reaction mixture
  4. customto yield a brown oil
  5. extractionThis oil was extracted with methylene chloride (×2)
  6. filtrationthe organic solution was filtered through silicone
  7. additiontreated
  8. filtrationfilter paper (Whatman 1PS)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-6b800643ebd5413a955dae9ff984f7c7
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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