Hydrochloric Acid → HCID 67099687, compound

HRID 1868643Notes

Reaction equation

HRID 1868643 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:13]([OH:15])=O)[CH2:12][CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[C:20]([O:28][CH2:29][CH3:30])(=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23].[Mg+2].[Cl-].[Cl-].C([O-])(=O)CC([O-])=O.Cl>C(#N)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:13]([CH:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:20]([O:28][CH2:29][CH3:30])=[O:27])=[O:15])[CH2:12][CH2:11][O:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 9084Malonate IonHCID 24386Thionyl ChlorideHCID 5360315Magnesium ChlorideHCID 670530593-(4-Chlorophenyl)tetrahydro-3-furancarboxylic acid

Product 1

HCID 67099687HCID 67099687, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

3-(4-Chlorophenyl)-tetrahydrofuran-3-carboxylic acid (375.2 mg, 1655 μmol) was mixed with thionyl chloride (1.21 mL, 16554 μmol) and heated at 70° C. for 3 hours. The solution was cooled, concentrated in vacuo, and pumped on under high vacuum for 3 hours. To a flame-dried round bottom flask containing diethyl malonate (0.25 mL, 1655 μmol) in ACN (3 mL), was added MgCl2 (158 mg, 1655 μmol). The resulting solution was cooled to 0° C. The reaction was then stirred for 15 minutes at 0° C. To the resulting mixture was slowly added TEA (0.48 mL, 3476 μmol), and the reaction was stirred at room temperature for 3 hours. The acid chloride intermediate in ACN (1.9 mL), was added to the malonate solution, and the resulting mixture was stirred at 50° C. for 13 hours. The reaction was then cooled and concentrated in vacuo to give a light yellow solid which was mixed with 1N HCl and EtOAc. The aqueous layer was extracted with EtOAc (2×), and the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica flash chromatography (10-30% EtOAc/hexane) gave the title compound as a light yellow oil. MS m/e=369.2 (M+H)+.

Workup

  1. temperatureThe solution was cooled
  2. concentrationconcentrated in vacuo
  3. temperatureThe resulting solution was cooled to 0° C
  4. stirringthe reaction was stirred at room temperature for 3 hours
  5. stirringthe resulting mixture was stirred at 50° C. for 13 hours
  6. temperatureThe reaction was then cooled
  7. concentrationconcentrated in vacuo
  8. customto give a light yellow solid which
  9. extractionThe aqueous layer was extracted with EtOAc (2×)
  10. dry with materialthe combined organic layers were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification by silica flash chromatography (10-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-ae4f6b4de37b4ec38ad6f59ed826733a
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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