Hydrogen Bromide → 2-(4-Bromo-3-propylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

HRID 1807802Notes

Reaction equation

HRID 1807802 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH2:18][CH2:19][CH3:20].[BrH:21].N([O-])=O.[Na+]>O1CCOCC1.O.[Cu]Br>[Br:21][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH2:18][CH2:19][CH3:20]

Participants

7

Reactant 3

HCID 260Hydrogen Bromide2×HCID 23668193Sodium NitriteHCID 592009542-(4-Amino-3-propyl-phenyl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

Product 1

HCID 768476502-(4-Bromo-3-propylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-olYield 50.3%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

2-(4-Amino-3-propylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (33.2 mmol, 10 g) was dissolved in dioxane (15 mL) and water (30 mL) was added. The suspension was heated to reflux then hydrobromic acid (48% weight in water, 149 mmol, 17 mL) was added drop wise via an addition funnel over a 20 minute period. The mixture was heated for a further 20 minutes before cooling to 0° C. A solution of sodium nitrite (33.2 mmol, 2.290 g) in water (30 mL) was added to the mixture over a 30 minute period and the mixture stirred at 0° C. for 30 minutes. A solution of copper (I) bromide (38.2 mmol, 5.48 g) in water (30 mL) and hydrobromic acid (48% weight in water, 149 mmol, 17 mL) was added drop wise to the mixture over a 20 minute period at 0° C. and the mixture was allowed to stir at 0° C. for 20 minutes. The mixture was warmed to 60° C. for 20 minutes then allowed to stir at room temperature overnight. The reaction mixture was extracted with diethyl ether (3×100 mL), the organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under vacuum. The resulting residue was purified by silica gel column chromatography (eluting with 10% ethyl acetate/90% heptane) to afford the title compound (6.1 g). MS (ESI) m/z 365.5 [M−H]

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux
  3. temperatureThe mixture was heated for a further 20 minutes
  4. stirringto stir at 0° C. for 20 minutes
  5. temperatureThe mixture was warmed to 60° C. for 20 minutes
  6. stirringto stir at room temperature overnight
  7. extractionThe reaction mixture was extracted with diethyl ether (3×100 mL)
  8. dry with materialthe organic phase was dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under vacuum
  11. customThe resulting residue was purified by silica gel column chromatography (eluting with 10% ethyl acetate/90% heptane)

Sources & evidence

ORD record
ord-30ec8ea2b5b0413683d35e8d2e2ff46f
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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