تفاعل #221028

معادلة التفاعل

1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone

Dimethyl disulfide

3,3-dimethyl-3-phenyl propionic acid

dry ice acetone

Lithium diisopropylamide

→

3-methyl-2-(methylsulfanyl)-3-phenylbutanoic acid

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGto stir for 30 minutes
2. 2
   workup.STIRRINGto stir for two days
3. 3
   درجة الحرارةwhile warming to room temperature
4. 4
   أخرىThe reaction is quenched by the addition of 10% aqueous hydrochloric acid solution
5. 5
   استخلاصextracted thrice with ethyl acetate
6. 6
   غسيلThe combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution
7. 7
   تجفيفdried over anhydrous sodium sulfite
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىto give a clear light brown oil which

الإجراء التجريبي

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(1 H)-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

المصدر