تفاعل #2155355

معادلة التفاعل

(S)-1-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-pyrrolidin-2-one

EtMgBr

→

(5S)-4-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-4-azaspiro[2.4]heptane

المردود 10.1%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGto stir at rt overnight
2. 2
   أخرىquenched with a mixture of 20 mL of water and 30 mL of ethyl acetate
3. 3
   workup.STIRRINGAfter stirring for 20 min
4. 4
   ترشيحthe mixture was filtered through a celite pad
5. 5
   استخلاصThe filtrate was extracted with ethyl acetate (30 mL×3)
6. 6
   تجفيفThe combined organic phases were dried over Na2SO4
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe residue was purified by a silica gel column chromatography (50:1(v/v) CH2Cl2/CH3OH)

الإجراء التجريبي

To a mixture of (S)-1-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-pyrrolidin-2-one (0.6 g, 2.82 mmol) in 20 mL of THF was added Ti(Oi-Pr)4 (2.56 mL, 8.45 mmol, d=0.937 g/L, Aldrich) via a syringe under nitrogen at rt. After stirring at rt for 30 min, EtMgBr (5.63 mL, 16.9 mmol, 3M ether solution, Aldrich) was added via a syringe pump over 3 hrs. The reaction was continued to stir at rt overnight, and then quenched with a mixture of 20 mL of water and 30 mL of ethyl acetate. After stirring for 20 min, the mixture was filtered through a celite pad. The filtrate was extracted with ethyl acetate (30 mL×3). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (50:1(v/v) CH2Cl2/CH3OH) to afford (5S)-4-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-4-azaspiro[2.4]heptane as pale yellow oil (64 mg, 10%).

المصدر