3,5-Difluorobenzaldehyde → (+/-)(3,5-Difluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanol

HRID 2246643Notes

Reaction equation

HRID 2246643 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([Mg]Br)=[CH:10][CH:9]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH:20]=[O:21]>C1COCC1>[F:16][C:17]1[CH:18]=[C:19]([CH:20]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)=[CH:9][CH:10]=2)[OH:21])[CH:22]=[C:23]([F:25])[CH:24]=1

Participants

4

Reactant 2

HCID 5881603,5-DifluorobenzaldehydeHCID 178419637HCID 178419637, compound

Product 1

HCID 57835854(+/-)(3,5-Difluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanolYield 88.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(2-Tetrahydro-2H-pyranoxy)phenylmagnesium bromide (0.5 M in THF, 35 mL, 17.5 mmol) was added to a solution of 3,5-difluorobenzaldehyde (1.95 g, 13.7 mmol) in THF (50 mL) slowly via syringe at −78° C. The reaction mixture was stirred at this temperature for 3 hours and then quenched with saturated NH4Cl (aqueous). The mixture was extracted with EtOAc (60 mL×2), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a colorless oil (3.9 g) as product M6.1, which was used directly in the next step.

Workup

  1. customquenched with saturated NH4Cl (aqueous)
  2. extractionThe mixture was extracted with EtOAc (60 mL×2)
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ab64632ce960418ebbac78bbdb96a357
Source dataset
uspto-grants-2010_03
Patent number
US07687526B2

Reaction notes

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