Acetic Anhydride → (5R,6RS)-6-[(RS)-Acetoxy-(5H-imidazo[2,1-a]isoindol-2-yl)-methyl]-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

HRID 638865노트

반응식

HRID 638865 반응식
[N:1]1[C:2]([CH:13]=[O:14])=[CH:3][N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=12.[Mg+2].[Br-].[Br-].[N+:18]([C:21]1[CH:39]=[CH:38][C:24]([CH2:25][O:26][C:27]([C:29]2[N:30]3[C@H:33]([S:34][CH:35]=2)[C@@H:32]([Br:36])[C:31]3=[O:37])=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19].[C:40](OC(=O)C)(=[O:42])[CH3:41]>C(OCC)(=O)C.C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:18]([C:21]1[CH:39]=[CH:38][C:24]([CH2:25][O:26][C:27]([C:29]2[N:30]3[C@H:33]([S:34][CH:35]=2)[C:32]([CH:13]([O:14][C:40](=[O:42])[CH3:41])[C:2]2[N:1]=[C:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[CH2:12][N:4]4[CH:3]=2)([Br:36])[C:31]3=[O:37])=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19]

참가 물질

9

반응물 4

HCID 7918Acetic AnhydrideHCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 222245345H-Imidazo[2,1-a]isoindole-2-carbaldehyde

생성물 1

HCID 68443556(5R,6RS)-6-[(RS)-Acetoxy-(5H-imidazo[2,1-a]isoindol-2-yl)-methyl]-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

시약·촉매·용매 4

HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

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온도
-20 °C

실험 절차

5H-Imidazo[2,1-a]isoindole-2-carbaldehyde (736.8 mg) was added to the dry acetonitrile (50 mL) solution of anhydrous MgBr2 (1.8 g) under a nitrogen atmosphere at room temperature. The dry THF solution (50 mL) of (5R,6S)-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (1.55 g) was added to the reaction mixture, cooled to −20° C., and triethylamine (1.34 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The mixture was stirred for 2 h at −20° C. and treated with acetic anhydride (0.76 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 18 h at 0° C. The mixture was diluted with ethyl acetate and washed with H2O, saturated sodium hydrogen carbonate, and brine. The organic layer was dried (MgSO4) and filtered through a pad of Celite. The pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then eluted with ethyl acetate-hexane (2/3˜1/1). The title compound was obtained as two diastereo mixture (5/1, a pale yellow amorphous solid, 1.8 g, 73%). 1H NMR (400 MHz, CDCl3) δ 2.02 (s, 0.84×3H), 2.27 (s, 0.16×3H), 4.89-4.94 (m, 2H), 5.29 (d, 1H, J=13.6 Hz), 5.47 (d, 1H, J=13.6 Hz), 6.18 (s, 0.16×1H), 6.40 (s, 0.84×1H), 6.42 (s, 0.84×1H), 6.94 (d, 0.16×1H, J=0.9 Hz), 7.18 (d, 0.16×1H, J=0.7 Hz), 7.35-7.48 (m, 3H), 7.51 (s, 0.84×1H), 7.60-7.64 (m, 2H), 7.79-7.83 (m, 1H), 8.23-8.27 (m, 2H).

후처리

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 18 h at 0° C
  3. washwashed with H2O, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered through a pad of Celite
  6. washThe pad was washed with ethyl acetate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. washeluted with ethyl acetate-hexane (2/3˜1/1)

출처 및 근거

ORD 기록
ord-56d5d8db14a34c0a903453dbd499ad59
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691842B2

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