Hexane → (+/-)-(tetrahydro-2H-pyran-4-yl)(4'-(trifluoromethyl)-[1, 1'-biphenyl]-4-yl)methanol

HRID 1427488Notes

Reaction equation

HRID 1427488 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[Li]CCCC.CCCCCC.[O:29]1[CH2:34][CH2:33][CH:32]([CH:35]=[O:36])[CH2:31][CH2:30]1>C1COCC1>[O:29]1[CH2:34][CH2:33][CH:32]([CH:35]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)=[CH:4][CH:3]=2)[OH:36])[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 8058HexaneHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 127123494-Bromo-4'-(trifluoromethyl)biphenylHCID 178418339Butyllithium

Product 1

HCID 67980970(+/-)-(tetrahydro-2H-pyran-4-yl)(4'-(trifluoromethyl)-[1, 1'-biphenyl]-4-yl)methanolYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A round bottom flask at −78° C. was charged with 4-bromo-4′-(trifluoromethyl)-1,1′-biphenyl (192 mg, 0.638 mmol) and THF (2.1 mL). nBuLi 2.5M in Hexane (281 μL, 702 mmol) was then added dropwise. The mixture stirred for one hour at −78° C. after which time, tetrahydro-2H-pyran-4-carbaldehyde (86 μL, 0.83 mmol) was added in one portion and mixture stirred for 30 minutes. Reaction mixture warmed up to 0° C. and stirred for an additional hour. Reaction quenched with ammonium chloride solution (aq. sat.) and extracted twice with ethyl acetate. Combined organic layers washed with brine, dried over sodium sulfate, filtered and concentrated to provide the crude oil. Purification by silica gel flash chromatography (MeOH/DCM) to give the title compound as a colorless oil (118 mg, 55.0%). MS (M): 336.

Workup

  1. additionwas added in one portion and mixture
  2. customReaction mixture
  3. stirringstirred for an additional hour
  4. customReaction
  5. customquenched with ammonium chloride solution (aq. sat.)
  6. extractionextracted twice with ethyl acetate
  7. washCombined organic layers washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide the crude oil
  12. customPurification by silica gel flash chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-7ce236efeb344f42bb020143e2b971b2
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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