Potassium Carbonate → 6-Bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinoline

HRID 1350137Notes

Reaction equation

HRID 1350137 reaction equation
C([O:8][C:9]1[C:18]([Br:19])=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11]([C:24]([F:27])([F:26])[F:25])=[CH:12][C:13]([O:20][CH:21]([CH3:23])[CH3:22])=[N:14]2)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CS(O)(=O)=O.C(O)(=O)C.O>[Br:19][C:18]1[C:9]([OH:8])=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[C:13]([O:20][CH:21]([CH3:23])[CH3:22])[CH:12]=[C:11]2[C:24]([F:27])([F:26])[F:25]

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 210943805-Benzyloxy-6-bromo-2-isopropoxy-4-(trifluoromethyl)quinoline

Product 1

HCID 1357977806-Bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinolineYield 92%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

A solution of 5-benzyloxy-6-bromo-2-isopropoxy-4-(trifluoromethyl)quinoline (13.5 g, 30.8 mmol) in 31 mL methanesulfonic acid and 31 mL acetic acid was stirred at rt for 10 h, whereupon it was poured in water (500 mL), neutralized with K2CO3 (ca. 75 g) and extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine (200 mL), dried over MgSO4, filtered and concentrated. Flash chromatography (2%–5% EtOAc:hexanes, gradient elution) afforded 9.9 g (92%) of 6-bromo-5-hydroxy-2-isopropoxy-4-(trifluoromethyl)quinoline, a yellow-brown oil. 1H NMR (400 MHz, CDCl3) δ 7.71 (d, 1H, J=9.1), 7.38 (d, 1H, J=9.1), 6.23 (s, 1H), 5.53 (sept, 1H, J=6.2), 1.41 (d, 6H, J=6.2).

Workup

  1. extractionextracted with EtOAc (3×200 mL)
  2. washThe combined organic layers were washed with brine (200 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washFlash chromatography (2%–5% EtOAc:hexanes, gradient elution)

Sources & evidence

ORD record
ord-2ce50820cd6d4c86a35a36b40bf07541
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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