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 590677ノート

反応式

HRID 590677 の反応式
[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

参加物

6

反応物 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

生成物 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-dicarboxylate収率 43%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-1058065be41d45cb90ab4502a9832ca7
出典データセット
uspto-grants-2016_01
特許番号
US09233974B2

反応ノート

読み込み中…