Hydrochloric Acid → HCID 67099779, compound

HRID 1868954Notes

Reaction equation

HRID 1868954 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl-].[Mg+2].[Cl-].[F:15][C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[C:23]1([C:29](O)=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.S(Cl)(Cl)(=O)=O.Cl>C(#N)C.CCOC(C)=O>[F:15][C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[C:23]1([C:29]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24648Sulfuryl chlorideHCID 5360315Magnesium ChlorideHCID 67100169HCID 67100169, compound

Product 1

HCID 67099779HCID 67099779, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of diethyl malonate (4.2 g, 26 mmol) in 50 mL ACN was stirred at 0° C. and treated with magnesium chloride (2.5 g, 26 mmol) in one portion and TEA (5.9 g, 58 mmol) dropwise. The mixture was stirred at room temperature for 2.5 hours. In a separate flask, a mixture of 4-(2,3-difluorophenyl)-tetrahydro-2H-pyran-4-carboxylic acid (6.4 g, 26 mmol) in sulfuryl dichloride (31 g, 264 mmol) was refluxed for 2 hours, then concentrated in vacuo. This residue was diluted with 30 mL ACN, and added to the malonate/magnesium chloride mixture dropwise. The resulting reaction was stirred at 50° C. for 1.5 hours. The mixture was cooled to room temperature, diluted with 200 mL EtOAc, neutralized to pH=5 with concentrated HCl, washed with H2O (2×50 mL), saturated NaCl (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography (10-20% EtOAc/hexane) to give the intermediate 3.3 g as pale yellow oil. MS m/e: (M+H)+ 385.

Workup

  1. stirringThe mixture was stirred at room temperature for 2.5 hours
  2. temperaturewas refluxed for 2 hours
  3. concentrationconcentrated in vacuo
  4. additionThis residue was diluted with 30 mL ACN
  5. additionadded to the malonate/magnesium chloride mixture dropwise
  6. customThe resulting reaction
  7. stirringwas stirred at 50° C. for 1.5 hours
  8. temperatureThe mixture was cooled to room temperature
  9. washwashed with H2O (2×50 mL), saturated NaCl (20 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by column chromatography (10-20% EtOAc/hexane)

Sources & evidence

ORD record
ord-4eeb30d6a63646cea9082bcfeaadb802
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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