Benzyl Bromide → HCID 86623497, compound

HRID 912995Notes

Reaction equation

HRID 912995 reaction equation
[F:1][CH:2]([F:15])[C:3]1N(C)[C:7]([CH:10]([OH:12])[CH3:11])=[C:6]([OH:13])[C:5](=[O:14])[CH:4]=1.[OH-:16].[Na+].[CH:18]1[CH:23]=[CH:22][C:21]([CH2:24]Br)=[CH:20][CH:19]=1>CO>[CH2:24]([O:13][C:6]1[C:5](=[O:14])[CH:4]=[C:3]([CH:2]([F:15])[F:1])[O:16][C:7]=1[CH:10]([OH:12])[CH3:11])[C:21]1[CH:22]=[CH:23][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 7498Benzyl Bromide2×HCID 14798Sodium Hydroxide2×HCID 25018907HCID 25018907, compound

Product 1

HCID 86623497HCID 86623497, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The 6-difluoromethyl-3-hydroxy-2-(1-hydroxy-ethyl)-1-methyl-1H-pyridin-4-one product obtained in the 2 experiments in step 1 above were combined together and dissolved in MeOH (50 mL). A 6.0 M NaOH solution (4 mL, 24 mmol) and BnBr (2.85 mL, 24 mL) were successively added at room temperature. The progress of the reaction was monitored by HPLC Method 1 as described above. After 1.5 hrs, HPLC analysis of the reaction mixture indicated presence of about 15% of unreacted starting material. Thus, another 1 mL of a 6.0 M NaOH solution and 1 mL of BnBr were added, and the mixture was refluxed for 1 hr. The mixture was cooled to room temperature, and evaporated to dryness. The residue was taken up in CH2Cl2, and the organic layer was washed with brine (40 mL). The aqueous brine layer was back washed with CH2Cl2 (40 mL). The organic fractions were combined, dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified by column chromatography on silica gel using a mixture of CH2Cl2 and MeOH (100/3, v/v) as eluant. Fractions rich in product were combined together, and concentrated to give 3-benzyloxy-6-difluoromethyl-2-(1-hydroxy-ethyl)-pyran-4-one (4.00 g) as a bright yellow oil. HPLC purity (peak area percent) of this material is 88.8% at λ=280 nm using HPLC Method 1 as described above.

Workup

  1. temperaturethe mixture was refluxed for 1 hr
  2. customevaporated to dryness
  3. washthe organic layer was washed with brine (40 mL)
  4. washThe aqueous brine layer was back washed with CH2Cl2 (40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by column chromatography on silica gel using
  9. additiona mixture of CH2Cl2 and MeOH (100/3
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-4f5c1067f23e446b933be5dade5d6683
Source dataset
uspto-grants-2011_09
Patent number
US08026261B2

Reaction notes

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