تفاعل #50037

معادلة التفاعل

5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone

product

5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone

borane THF

→

title compound

3-Methyl-5-(1-methyl-2(S)-pyrrolidinyl)isoxazole

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was heated
2. 2
   درجة الحرارةat reflux for two hours
3. 3
   أخرىAfter removal of THF under vacuum
4. 4
   workup.ADDITIONa solution of formaldehyde (10.0 mL) and formic acid (5.0 mL) was carefully added
5. 5
   درجة الحرارةthe reaction mixture was refluxed for one hour
6. 6
   workup.ADDITIONEthyl acetate (300 mL) was added
7. 7
   workup.ADDITIONfollowed by the addition of sodium carbonate until basic
8. 8
   أخرىThe organic layer was decanted
9. 9
   غسيلthe residue was washed with ethyl acetate (4×20 mL)
10. 10
    تجفيفThe combined organic solvents were dried over sodium carbonate
11. 11
    أخرىThe solvent was evaporated
12. 12
    workup.DISTILLATIONthe residue was distilled (bp. ~150° C./~50 mm Hg)

الإجراء التجريبي

To a solution of crude 5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone (5.33 g, 32.1 mmol, the product of step 13b) in THF (50 mL) was added borane-THF (99.5 mL, 1.0M, 99.5 mmol) slowly at room temperature. The reaction mixture was heated at reflux for two hours. After removal of THF under vacuum, a solution of formaldehyde (10.0 mL) and formic acid (5.0 mL) was carefully added, and the reaction mixture was refluxed for one hour. Ethyl acetate (300 mL) was added, followed by the addition of sodium carbonate until basic. The organic layer was decanted, and the residue was washed with ethyl acetate (4×20 mL). The combined organic solvents were dried over sodium carbonate. The solvent was evaporated, and the residue was distilled (bp. ~150° C./~50 mm Hg) to give the title compound (3.12 g, 59%; 24% overall yield). The compound was further purified by HPLC chromatography (CHCl3 /MeOH, 20:1 and 10:1). HPLC (analytical Chiralark OD column) analysis indicated >99% ee. [α]D23° =-13.1° (c 0.9, MeOH). MS (DCl/NH3) m/e: 153 (M+H)+. 1H NMR (CDCl3) δ 1.80-2.00 (m, 3H), 1.99 (br s, 1H, NH), 2.14-2.21 (m, 1H), 2.28 (s, 3H), 2.96-3.16 (m, 2H), 4.32 (dd, 1H), 5.95 (s, 1H).

المصدر