Hydrochloric Acid → HCID 86623498, compound

HRID 1187462Notes

Reaction equation

HRID 1187462 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH:16]([F:18])[F:17])[O:11][C:10]=1[CH:19](O)[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)Cl.CCOC(C)=O.Cl>CC#N.[Zn]>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH:16]([F:18])[F:17])[O:11][C:10]=1[CH2:19][CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 86623497HCID 86623497, compound

Product 1

HCID 86623498HCID 86623498, compoundYield 50.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 3-benzyloxy-6-difluoromethyl-2-(1-hydroxy-ethyl)-pyran-4-one (1.30 g, 4.38 mmol), described in step 2 of Example 10, in CH3CN (14 mL) cooled in an ice-salt bath was added a solution of SOCl2 (0.45 mL, 5.44 mmol) in CH3CN (0.5 mL). The reaction mixture was stirred at ice-cold temperature for 9 hrs. The progress of the reaction was monitored by TLC using a mixture of hexanes and EtOAc (1/1, v/v) as eluant. Volatile materials were removed in vacuo, and ice-cold i-PrOH (15 mL) was added, and the mixture was cooled in an ice-salt bath. Then Zn dust (600 mg, 9 mmol) was added followed by concentrated HCl (1.1 mL). After 20 min, the reaction mixture was filtered through a CELITE™ bed, and the filtrate was evaporated to dryness. The residue was taken up in CH2Cl2 (100 mL), and the organic layer was washed with brine (2×30 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residual oil was purified by column chromatography on silica gel using a mixture of hexanes and EtOAc (10/3, v/v) as eluant. Fractions rich in product were combined together, and concentrated to give 3-benzyloxy-6-difluoromethyl-2-ethyl-pyran-4-one (0.62 g) as a yellow oil. HPLC purity (peak area percent) of this material is 99.0% at λ=280 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, DMSO-D6) δ (ppm): 7.30-7.40 (m, 5H), 7.06 (t, J=52.7 Hz, 1H, CF2H), 6.76 (s, 1H), 5.07 (s, 2H), 2.56 (q, J=7.4 Hz, 1H, CH2CH3), 0.97 (t, J=7.5 Hz, 3H, CH2CH3).

Workup

  1. temperaturecooled in an ice-salt bath
  2. customVolatile materials were removed in vacuo, and ice-cold i-PrOH (15 mL)
  3. additionwas added
  4. temperaturethe mixture was cooled in an ice-salt bath
  5. waitAfter 20 min
  6. filtrationthe reaction mixture was filtered through a CELITE™ bed
  7. customthe filtrate was evaporated to dryness
  8. washthe organic layer was washed with brine (2×30 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residual oil was purified by column chromatography on silica gel using
  13. additiona mixture of hexanes and EtOAc (10/3
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-b42619c772da4b8ab049b40e9f27c29d
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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