Water → 4-[Cyclohexylidene(4-hydroxyphenyl)methyl]-2-fluorobenzaldehyde

HRID 1716048Notes

Reaction equation

HRID 1716048 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[O:17]CCO2)=[C:9]([F:18])[CH:8]=1.[CH:19]1([C:25]([C:27]2[CH:32]=[CH:31][C:30]([O:33]COC)=[CH:29][CH:28]=2)=O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.O>C1COCC1>[C:19]1(=[C:25]([C:27]2[CH:28]=[CH:29][C:30]([OH:33])=[CH:31][CH:32]=2)[C:7]2[CH:12]=[CH:11][C:10]([CH:13]=[O:17])=[C:9]([F:18])[CH:8]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

6

Reactant 4

HCID 962WaterHCID 219386012-(4-Bromo-2-Fluorophenyl)-1,3-DioxolaneHCID 68654452Cyclohexyl[4-(methoxymethoxy)phenyl]methanoneHCID 178418339Butyllithium

Product 1

HCID 860299754-[Cyclohexylidene(4-hydroxyphenyl)methyl]-2-fluorobenzaldehydeYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (1.6 M in hexanes, 1.33 mL, 2.13 mmol) was added dropwise to 88 (503 mg, 2.04 mmol) dissolved in anhydrous THF (25 mL) at −78° C. The reaction mixture was stirred for 20 min and 87 (460 mg, 1.85 mmol), dissolved in THF (25 mL), was added dropwise. The mixture was warmed slowly to RT and stirred overnight. Water (150 mL) was added and the mixture was extracted with ether (3×100 mL). The combined ethereal extracts were washed with water (200 mL), brine (200 mL), dried (MgSO4), and concentrated under reduced pressure. The resulting crude oil was taken up in a mixture of EtOH (10 mL) and 12 M HCl (2 mL) and refluxed for 2 h. Removal of solvent and flash chromatography (20:1 to 5:1 hexanes:EtOAc) afforded 200 mg (35%) of 89 as a white solid. 1H NMR (400 MHz, CDCl3): δ 1.60 (br s, 6H), 2.23 (m, 4H), 6.00 (s, 1H), 6.79 (d, J=8.2 Hz, 2H), 6.89-6.95 (m, 3H), 7.02 (d, J=7.9 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 10.28 (s, 1H).

Workup

  1. additionwas added dropwise
  2. stirringstirred overnight
  3. extractionthe mixture was extracted with ether (3×100 mL)
  4. washThe combined ethereal extracts were washed with water (200 mL), brine (200 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. additionThe resulting crude oil was taken up in a mixture of EtOH (10 mL) and 12 M HCl (2 mL)
  8. temperaturerefluxed for 2 h
  9. customRemoval of solvent and flash chromatography (20:1 to 5:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-363b5f3b53fd482c873aa8f1c5adede7
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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