Sodium hydride → 7-[(R)-2-oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester

HRID 2052922

반응식

HRID 2052922 반응식
[H-].[Na+].[O:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]P(=O)(OC)OC.[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][N:26]1[C:31](=[O:32])[CH2:30][CH2:29][CH2:28][C@@H:27]1[CH:33]=O>C1COCC1>[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][N:26]1[C@@H:27](/[CH:33]=[CH:5]/[C:4](=[O:3])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:28][CH2:29][CH2:30][C:31]1=[O:32]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 580181Dimethyl (2-oxoheptyl)phosphonateHCID 865952957-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester

생성물 1

HCID 690237087-[(R)-2-oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester수율 85.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Sodium hydride (60% dispersion in oil, 8.8 mg, 0.22 mmol) was added to a solution of dimethyl 2-oxoheptylphosphonate (52 mg, 0.23 mmol) in THF (1 mL) at 0° C. After 10 min at 0° C., the solution was allowed to warm to rt. After 1 h at rt, the solution was recooled to 0° C. and 7-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (crude from previous reaction, ˜0.22 mmol) in THF (1 mL) was added via cannula. The reaction was allowed to warm to rt. After 18.5 h at rt, the reaction was quenched with aqueous acetic acid (50%, 5 mL) and extracted with EtOAc (3×10 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2<2% MeOH/CH2Cl2, gradient) afforded 68 mg (85%) of 7-[(R)-2-oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester.

후처리

  1. waitAfter 1 h at rt
  2. customwas recooled to 0° C.
  3. temperatureto warm to rt
  4. waitAfter 18.5 h at rt
  5. customthe reaction was quenched with aqueous acetic acid (50%, 5 mL)
  6. extractionextracted with EtOAc (3×10 mL)
  7. washThe combined organic phase was washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  8. dry with materialthen dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2<2% MeOH/CH2Cl2, gradient)

출처 및 근거

ORD 기록
ord-5f39fa0221234fcdb013fb706325e838
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07326716B2

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