تفاعل #79583

معادلة التفاعل

tert-Butyl bromoacetate

tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Sodium hydride

→

title compound

tert-Butyl (3R)-3-(2-tert-butoxy-2-oxoethoxy)pyrrolidine-1-carboxylate

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe mixture was heated
2. 2
   درجة الحرارةunder reflux for 18 hours
3. 3
   درجة الحرارةcooled
4. 4
   تركيزconcentrated under reduced pressure
5. 5
   أخرىThe residue was partitioned between ethyl acetate and water
6. 6
   أخرىthe phases separated
7. 7
   تجفيفThe organic layer was dried (MgSO4)
8. 8
   أخرىevaporated under reduced pressure
9. 9
   أخرىThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80)

الإجراء التجريبي

Sodium hydride (704 mg, 60% in mineral oil, 17.6 mmol) was added to an ice-cooled solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (J. Med. Chem. 1998, 41(25), 4983) (5 g, 26.7 mmol) in tetrahydrofuran (100 ml), and the mixture was allowed to warm to room temperature and stirred for 20 minutes. tert-Butyl bromoacetate (5.2 g, 26.7 mmol) was added and the mixture was heated under reflux for 18 hours, then cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the phases separated. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80) to afford the title compound, 1.95 g.

المصدر