Phosphorus oxybromide → HCID 86014622, compound

HRID 523756Notes

Reaction equation

HRID 523756 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](O)[C:11]2[C:16]([C:17]=1[OH:18])=[C:15]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].P(Br)(Br)([Br:28])=O.C(=O)(O)[O-].[Na+]>C(#N)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([Br:28])[C:11]2[C:16]([C:17]=1[OH:18])=[C:15]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 24613Phosphorus oxybromideHCID 516892Sodium BicarbonateHCID 178450845HCID 178450845, compound

Product 1

HCID 86014622HCID 86014622, compoundYield 98.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

411 mg of 1,4-Dihydroxy-5-phenyl-isoquinoline-3-carboxylic acid butyl ester, from Example D-39c isomer B, was suspended in 15 ml of anhydrous acetonitrile. 2.0 g of phosphorous oxybromide was added and the reaction mixture was heated to reflux for 3.5 h. The reaction mixture was cooled and poured into 75 ml of 0° C. saturated aqueous sodium bicarbonate solution. The mixture was stirred for 5 min and then extracted with 75 ml portions of ethyl acetate three times. The combined organic fractions were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue (434 mg) was purified by chromatography on silica gel using a gradient of 0 to 25% ethyl acetate in hexanes to elute the product as one major fraction. 480 mg of the desired product was obtained; MS (+): m/z 422.02 (M+23)

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 3.5 h
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with 75 ml portions of ethyl acetate three times
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue (434 mg) was purified by chromatography on silica gel using a gradient of 0 to 25% ethyl acetate in hexanes
  9. washto elute the product as one major fraction

Sources & evidence

ORD record
ord-38481ed088a042d099947279ebcef7f4
Source dataset
uspto-grants-2016_05
Patent number
US09339527B2

Reaction notes

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