Glycerol → 8-Bromo-5-fluoroquinoline

HRID 2242007Notes

Reaction equation

HRID 2242007 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].[N+]([C:13]1[CH:18]=CC(O)=C[CH:14]=1)([O-])=O.OCC(CO)O.S(=O)(=O)(O)O>O>[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[C:5]2[C:3]=1[N:4]=[CH:18][CH:13]=[CH:14]2

Participants

6

Reactant 4

HCID 753GlycerolHCID 9804-Nitrophenol4×HCID 1118Sulfuric AcidHCID 27733172-Bromo-5-fluoroaniline

Product 1

HCID 145483478-Bromo-5-fluoroquinoline

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Alternatively, 8-bromo-5-fluoroquinoline was prepared by adding a warm mixture containing 2-bromo-5-fluoroaniline (100 g, 1.0 eq), 4-nitrophenol (40 g, 0.54 eq), and glycerol (97 g, 2.0 eq) over 1.5 hours to sulfuric acid (267 ml) and water (114 mL) at 140-150° C. The initial mixture showed 37.8% 4-nitrophenol by relative HPLC area %. Samples showed 4.7% 4-nitrophenol immediately after adding 50% of mixed starting materials and 5.0% immediately after adding all of the materials. The yield upon workup was 87.5%, with total impurities 0.29%. Addition of less (0.46 eq, 34 g) 4-nitrophenol also successfully produced the intermediate of interest at acceptable yield.

Workup

  1. additionby adding a warm mixture
  2. additionafter adding 50%
  3. additionof mixed
  4. additionafter adding all of the materials
  5. customThe yield upon workup
  6. customalso successfully produced the intermediate of interest at acceptable yield

Sources & evidence

ORD record
ord-d4a98501eb504664b088dd190aa0db37
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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