Thionyl Chloride → HCID 178451154, compound

HRID 1909871Notes

Reaction equation

HRID 1909871 reaction equation
[CH2:1]([O:5][C:6]([C@@H:8]1[CH2:13][CH2:12][C@H:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].S(Cl)(Cl)=O.[CH3:21][Li].[Cl-].[NH4+]>CN(C=O)C.[Cu](I)I.C(OCC)(=O)C.CO.C1COCC1.C(OCC)C>[C:14]([C@@H:11]1[CH2:10][CH2:9][C@H:8]([C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[O:7])[CH2:13][CH2:12]1)(=[O:16])[CH3:21]

Participants

11

Reactant 4

HCID 24386Thionyl ChlorideHCID 25517Ammonium ChlorideHCID 178418348HCID 178418348, compoundHCID 178451161HCID 178451161, compound

Product 1

HCID 178451154HCID 178451154, compound

Reagents, catalysts & solvents 6

HCID 6228DimethylformamideCatalystHCID 83717Copper iodideCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of cis-4-(butoxycarbonyl)cyclohexane carboxylic acid (3.3 g) and thionyl chloride (13 mL) was added DMF (2 drops), followed by stirring at 50° C. for 0.5 hours. The reaction mixture was concentrated under reduced pressure and azeotroped with toluene to obtain a residue. A mixture of copper iodide (5.2 g) and THF (13 mL) was stirred at an internal temperature of −40° C. under an argon atmosphere. To the reaction mixture was added dropwise a diethyl ether solution (1.1 M, 55 mL) of methyl lithium at an internal temperature of −30 to −40° C. over about 15 minutes, followed by stirring at the same temperature for 1 hour. The reaction mixture was cooled to an internal temperature of −60° C., and the THF solution (10 mL) of the above-described residue was added dropwise thereto at an internal temperature of −50 to −60° C. over about 5 minutes. The mixture was stirred at the same temperature for 0.5 hours, and methanol (15 mL) was added dropwise thereto, followed by warming to room temperature. To the reaction mixture were added a saturated aqueous ammonium chloride solution and ethyl acetate, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined, washed with a saturated aqueous ammonium chloride solution and saturated brine, dried over anhydrous magnesium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain butyl cis-4-acetylcyclohexane carboxylate (2.2 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customazeotroped with toluene
  3. customto obtain a residue
  4. stirringwas stirred at an internal temperature of −40° C. under an argon atmosphere
  5. stirringby stirring at the same temperature for 1 hour
  6. temperatureThe reaction mixture was cooled to an internal temperature of −60° C.
  7. waitat an internal temperature of −50 to −60° C. over about 5 minutes
  8. stirringThe mixture was stirred at the same temperature for 0.5 hours
  9. temperatureby warming to room temperature
  10. extractionthe aqueous layer was extracted with ethyl acetate
  11. washwashed with a saturated aqueous ammonium chloride solution and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-710ddb17fc4944118bb2d3d251e3bcb8
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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