Dimethyl Disulfide → HCID 11816956, compound

HRID 1865752Notes

Reaction equation

HRID 1865752 reaction equation
[CH3:1][C:2]([CH3:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].C(=O)=O.CC(C)=O.C([N-]C(C)C)(C)C.[Li+].CN1CCCN(C)C1=O.[CH3:38][S:39]SC>O1CCCC1>[CH3:1][C:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:13])[CH:3]([S:39][CH3:38])[C:4]([OH:6])=[O:5]

Participants

7

Reactant 5

HCID 12232Dimethyl DisulfideHCID 13890beta-Phenylisovaleric acidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardice

Product 1

HCID 11816956HCID 11816956, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In accordance with a modified literature procedure (Pfeffer, P. E.; Silbert, L. S.; Chirinko, J. M. J. Org. Chem. 37(3), 1972, 451-458), a solution of 3,3-dimethyl-3-phenyl propionic acid (0.50 g, 2.8 mmol, from Reference Example 22) in tetrahydrofuran (5 mL) is cooled to −40° C. (dry ice/acetone) while stirring under a nitrogen atmosphere. Lithium diisopropylamide (Aldrich, 2.0 M solution in tetrahydrofuran/ethylbenzene/heptane, 3.1 mL, 6.2 mmol) is added dropwise via syringe, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, 0.37 mL, 3.1 mmol). The reaction mixture is then allowed to warm to room temperature and to stir for 30 minutes before being re-cooled to 0° C. (ice water bath). Dimethyl disulfide (0.38 mL, 4.2 mmol) is then added neat via syringe and the reaction mixture is allowed to stir for two days while warming to room temperature. The reaction is quenched by the addition of 10% aqueous hydrochloric acid solution and extracted thrice with ethyl acetate. The combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulfite, and concentrated under reduced pressure. Flash chromatography (silica gel, hexanes/dichloromethane/methanol) is performed to give a clear light brown oil which solidified upon standing (0.54 g, 86%). TOF MS (ES−): (M−H)=222.9

Workup

  1. stirringto stir for 30 minutes
  2. stirringto stir for two days
  3. temperaturewhile warming to room temperature
  4. customThe reaction is quenched by the addition of 10% aqueous hydrochloric acid solution
  5. extractionextracted thrice with ethyl acetate
  6. washThe combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfite
  8. concentrationconcentrated under reduced pressure
  9. customto give a clear light brown oil which

Sources & evidence

ORD record
ord-d1aaf9b77e5f4433bb12ef11554d240e
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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