Hydrochloric Acid → (2RS,4SR)-4-(3,5-difluorophenyl)-4-hydroxy-2-methyltetrahydropyran

HRID 1492152Notes

Reaction equation

HRID 1492152 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[C:6]([F:8])[CH:7]=1.[Mg].[CH3:11][CH:12]1[CH2:17][C:16](=[O:18])[CH2:15][CH2:14][O:13]1.Cl>BrCCBr.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:16]2([OH:18])[CH2:15][CH2:14][O:13][CH:12]([CH3:11])[CH2:17]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1363131-Bromo-3,5-difluorobenzeneHCID 5462224MagnesiumHCID 103744342-Methyltetrahydro-4H-pyran-4-one

Product 1

HCID 22413801(2RS,4SR)-4-(3,5-difluorophenyl)-4-hydroxy-2-methyltetrahydropyranYield 36%

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A Grignard reagent was prepared from 3,5-difluorobromobenzene (0.772 g), 1,2-dibromoethane (2 drops), magnesium (0.106 g) and THF (5 ml). The mixture was stirred at ambient temperature for 15 minutes and then heated to 50° C. for 15 minutes. The mixture was allowed to recool to ambient temperature and a solution of 2-methyltetrahydropyran-4-one (J. Amer. Chem. Soc., 1982, 104, 4666) in THF (1 ml) was added dropwise. The mixture was stirred at ambient temperature for 1 hour. The mixture was poured into dilute aqueous hydrochloric acid and extracted with diethyl ether. The organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 9:1 v/v mixture of methylene chloride and diethyl ether as eluent. There was thus obtained a less polar isomer, (2RS,4SR)-4-(3,5-difluorophenyl)-4-hydroxy-2-methyltetrahydropyran (0.25 g, 36%), having the 2-methyl and 4-hydroxy substituents in a trans-relationship.

Workup

  1. temperatureheated to 50° C. for 15 minutes
  2. customto recool to ambient temperature
  3. stirringThe mixture was stirred at ambient temperature for 1 hour
  4. extractionextracted with diethyl ether
  5. washThe organic phase was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by column chromatography
  9. additiona 9:1 v/v mixture of methylene chloride and diethyl ether as eluent

Sources & evidence

ORD record
ord-c0ab9cbfc4914979aed0420a861d491f
Source dataset
uspto-grants-1994_12
Patent number
US05373007

Reaction notes

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