Cesium carbonate → (2S,5S)-1-tert-butyl 2-(3-(2-((2S,5S)-1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carbonyloxy)acetyl)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate

HRID 590677노트

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HRID 590677 반응식
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([C@@H:41]([CH3:44])[CH2:42][CH3:43])[C:7]([N:9]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]([O:17][CH2:18][C:19]([C:21]1[CH:22]=[CH:23][C:24]2[C:33]3[CH:32]=[C:31]4[CH2:34][CH2:35][CH:36](Br)[C:37](=[O:38])[C:30]4=[CH:29][C:28]=3[O:27][CH2:26][C:25]=2[CH:40]=1)=[O:20])=[O:16])=[O:8])=[O:4].[C:45]([O:49][C:50]([N:52]1[C@@H:56]([CH3:57])[CH2:55][CH2:54][C@H:53]1[C:58]([OH:60])=[O:59])=[O:51])([CH3:48])([CH3:47])[CH3:46].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CCOC(C)=O>[CH3:57][C@@H:56]1[N:52]([C:50]([O:49][C:45]([CH3:46])([CH3:48])[CH3:47])=[O:51])[C@H:53]([C:58]([O:60][CH:36]2[CH2:35][CH2:34][C:31]3=[CH:32][C:33]4[C:24]5[CH:23]=[CH:22][C:21]([C:19](=[O:20])[CH2:18][O:17][C:15]([C@@H:10]6[CH2:11][CH2:12][C@H:13]([CH3:14])[N:9]6[C:7](=[O:8])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[C@@H:41]([CH3:44])[CH2:42][CH3:43])=[O:16])=[CH:40][C:25]=5[CH2:26][O:27][C:28]=4[CH:29]=[C:30]3[C:37]2=[O:38])=[O:59])[CH2:54][CH2:55]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 15516206(5S)-1-(tert-Butoxycarbonyl)-5-methyl-L-prolineHCID 86723609(2S,5S)-2-(9-Bromo-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl 1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carboxylate

생성물 1

HCID 86723611(2S,5S)-1-tert-butyl 2-(3-(2-((2S,5S)-1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carbonyloxy)acetyl)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate수율 43%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

To a solution of (2S,5S)-2-(9-bromo-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl 1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carboxylate (5.95 g, 8.88 mmol) in THF (60 mL) was added (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (3.05 g, 13.3 mmol) and Cs2CO3 (2.31 g, 7.09 mmol). The resulting solution was heated to 50° C. for 18 h. The solution was cooled to room temperature and diluted with EtOAc and washed with aqueous HCl (0.5 M). The aqueous layer was backextracted with EtOAc (2×), and the combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by column chromatography (SiO2, 25-100% EtOAc (5% MeOH)/Hexanes) to provide (2S,5S)-1-tert-butyl 2-(3-(2-((2S,5S)-1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carbonyloxy)acetyl)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate (3.116, 43% over 2 steps) as a orange foam. LCMS-ESI+: calc'd for C44H55N3O12: 817.38 (M+). Found: 817.65 (M+).

후처리

  1. temperatureThe solution was cooled to room temperature
  2. washwashed with aqueous HCl (0.5 M)
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude oil was purified by column chromatography (SiO2, 25-100% EtOAc (5% MeOH)/Hexanes)

출처 및 근거

ORD 기록
ord-1058065be41d45cb90ab4502a9832ca7
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233974B2

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