Formaldehyde → (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate

HRID 340918

반응식

HRID 340918 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][C@H:5]([NH:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C:6]([OH:8])=[O:7].[O:20]=[C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])N1C(OCC)=O.C=O.[CH3:38]C1C=CC(S(O)(=O)=O)=CC=1>CN1C(=O)CCC1.CCOC(C)=O.C1(C)C=CC=CC=1.CCOCC>[O:20]=[C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:1]1[CH2:2][CH2:3][CH2:4][C@H:5]1[C:6](=[O:8])[O:7][CH2:38][N:9]1[C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:11]

참가 물질

9

반응물 4

HCID 712FormaldehydeHCID 6101p-Toluenesulfonic acidHCID 31187N-CarbethoxyphthalimideHCID 7010490N-alpha-Benzyloxycarbonyl-L-ornithine

생성물 1

HCID 54380156(S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate수율 76%

시약·촉매·용매 4

HCID 1140Toluene용매2회HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
150 °C

실험 절차

A mixture of (S)-5-amino-2-(benzyloxycarbonylamino)pentanoic acid (10.0 g, 37.56 mmol), ethyl 1,3-dioxoisoindoline-2-carboxylate (9.04 g, 41.28 mmol) in NMP (40.0 mL) was heated to 150° C. for 30 min in 4 microwave reaction tubes. The mixture was diluted with EtOAc (500 mL). The organic layer washed with water (100 mL×2), brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give an oil, which was dissolved in toluene. To this toluene solution was added paraformaldehyde, PTSA and molecular sieves (3 Å) and the mixture was heated to 150° C. for 20 min. The mixture was diluted with ether (800 mL), washed with NaHCO3, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate (11.6 g, 76% for 2 steps).

후처리

  1. washThe organic layer washed with water (100 mL×2), brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give an oil, which
  6. temperaturethe mixture was heated to 150° C. for 20 min
  7. washwashed with NaHCO3, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude was purified on silica gel column
  12. additiona mixture of EtOAc and hexanes

출처 및 근거

ORD 기록
ord-d905ed731ce9460db2768a56206d4a4c
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895582B2

연결된 노트

불러오는 중…