Phosphorus oxybromide → 1-Bromo-6-(2-ethyl-6-methyl-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester

HRID 706186Notes

Reaction equation

HRID 706186 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])=[CH:15][C:14]([O:19][C:20]1[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:27][CH3:28])=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].P(Br)(Br)([Br:32])=O>CC#N>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([Br:32])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:27][CH3:28])=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 24613Phosphorus oxybromideHCID 178450851HCID 178450851, compound

Product 1

HCID 866170731-Bromo-6-(2-ethyl-6-methyl-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl esterYield 34.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-(2-Ethyl-6-methyl-phenoxy)-1,4-dihydroxy-isoquinoline-3-carboxylic acid butyl ester (2.83 mmol, 1.12 g), POBr3 (11 mmol, 3.19 g), MeCN (20 mL) was refluxed gently with stirring for 1 h before it was concentrated in vacuo. The residue was dissolved in CHCl3 (50 mL). Water (10 mL) and subsequently small portions of NaHCO3 (6 g) were added with stirring. The mixture was stirred for 30 min at ambient temperature before it was filtered through a pad of celite. The filtrate was dried over MgSO4. Concentration and purification of the residue by flash column chromatography on silica gel using CH2Cl2 as the eluent gave the title compound as a tan oil (450 mg); MS-(+)-ion: M+1, 79Br/81Br=458.4 and 460.6.

Workup

  1. temperaturewas refluxed gently
  2. concentrationwas concentrated in vacuo
  3. dissolutionThe residue was dissolved in CHCl3 (50 mL)
  4. additionWater (10 mL) and subsequently small portions of NaHCO3 (6 g) were added
  5. stirringwith stirring
  6. stirringThe mixture was stirred for 30 min at ambient temperature before it
  7. filtrationwas filtered through a pad of celite
  8. dry with materialThe filtrate was dried over MgSO4
  9. concentrationConcentration and purification of the residue by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-78da7146ad6645788fffc7723bb2d776
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

Loading…