반응 #50037

반응 방정식

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

용매

THF

반응 조건

후처리

1. 1
   온도The reaction mixture was heated
2. 2
   온도at reflux for two hours
3. 3
   기타After 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
   온도the 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
   기타The organic layer was decanted
9. 9
   세척the residue was washed with ethyl acetate (4×20 mL)
10. 10
    건조The combined organic solvents were dried over sodium carbonate
11. 11
    기타The solvent was evaporated
12. 12
    workup.DISTILLATIONthe residue was distilled (bp. ~150° C./~50 mm Hg)

실험 절차

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).

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