1-Bromo-4-fluorobenzene → 4,4'-Difluorobenzhydryl alcohol

HRID 1818886Notes

Reaction equation

HRID 1818886 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][CH:3]=1.C([Li])CCC.[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=1.[Cl-].[NH4+]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:19]([C:18]2[CH:21]=[CH:22][C:15]([F:14])=[CH:16][CH:17]=2)[OH:20])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 25517Ammonium ChlorideHCID 680234-FluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 1230494,4'-Difluorobenzhydryl alcoholYield 37.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Fluorobromobenzene (19.26 g) in tetrahydrofuran (280 ml) was cooled to −78° C. and n-butyllithium (2.66 M n-hexane solution; 42 ml) was added thereto dropwise over 10 minutes or more while agitating. The reaction mixture was agitated for 1 hour while keeping the temperature. Then, 4-fluorobenzaldehyde (12.42 g) was added thereto dropwise over 10 minutes or more while agitating. The reaction mixture was agitated for 2 hours while keeping the temperature. Subsequently, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then brought to room temperature. The tetrahydrofuran was removed under reduced pressure, and the resultant residue was extracted with ethyl acetate. The organic layer washed with brine, dried with sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography to thereby obtain the subject compound (8.28 g).

Workup

  1. stirringThe reaction mixture was agitated for 1 hour
  2. stirringdropwise over 10 minutes or more while agitating
  3. stirringThe reaction mixture was agitated for 2 hours
  4. customwas then brought to room temperature
  5. customThe tetrahydrofuran was removed under reduced pressure
  6. extractionthe resultant residue was extracted with ethyl acetate
  7. washThe organic layer washed with brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3e1d8e6087b44ea59848e64bc031f623
Source dataset
uspto-grants-2009_10
Patent number
US07601734B2

Reaction notes

Loading…