Borane;tetrahydrofuran → 3-Methyl-5-(1-methyl-2(S)-pyrrolidinyl)isoxazole

HRID 21759

반응식

HRID 21759 반응식
[CH3:1][C:2]1[CH:6]=[C:5]([C@H:7]2[NH:11][C:10](=O)[CH2:9][CH2:8]2)[O:4][N:3]=1.B.[CH2:14]1COCC1>C1COCC1>[CH3:1][C:2]1[CH:6]=[C:5]([C@@H:7]2[CH2:8][CH2:9][CH2:10][N:11]2[CH3:14])[O:4][N:3]=1

참가 물질

4

반응물 2

HCID 2723981Borane;tetrahydrofuranHCID 11094992(5S)-5-(3-methyl-1,2-oxazol-5-yl)pyrrolidin-2-one2회

생성물 1

HCID 1193803-Methyl-5-(1-methyl-2(S)-pyrrolidinyl)isoxazole

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for two hours
  3. customAfter removal of THF under vacuum
  4. additiona solution of formaldehyde (10.0 mL) and formic acid (5.0 mL) was carefully added
  5. temperaturethe reaction mixture was refluxed for one hour
  6. additionEthyl acetate (300 mL) was added
  7. additionfollowed by the addition of sodium carbonate until basic
  8. customThe organic layer was decanted
  9. washthe residue was washed with ethyl acetate (4×20 mL)
  10. dry with materialThe combined organic solvents were dried over sodium carbonate
  11. customThe solvent was evaporated
  12. distillationthe residue was distilled (bp. ~150° C./~50 mm Hg)

출처 및 근거

ORD 기록
ord-5e3f65c95f1e4fcb8f168440c11ecc3d
출처 데이터셋
uspto-grants-1995_06
특허 번호
US05424444

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