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Citric Acid → [(S*)-2-(3-Benzyloxy-phenyl)-1-((2S*,4R*)-4-methyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester

HRID 1432334
ノート
印刷プレビュー

反応式

HRID 1432334 の反応式
[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C@@H:24]1[CH:28]=[CH:27][C:26](=[O:29])[O:25]1)[CH2:9][C:10]1[CH:15]=[CH:14][C:13](OCC2C=CC=CC=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:31]N1C(=O)N(C)CCC1.[Li].C[Si]([N-][Si](C)(C)C)(C)C.CI.[C:52]([OH:56])(=O)[CH2:53][CH3:54].[C:57](O)(=O)[CH2:58][C:59](CC(O)=O)([C:61](O)=O)O>C1COCC1.O>[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C@@H:24]1[CH2:28][C@@H:27]([CH3:31])[C:26](=[O:29])[O:25]1)[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:56][CH2:52][C:53]2[CH:54]=[CH:61][CH:59]=[CH:58][CH:57]=2)[CH:15]=1)([CH3:4])([CH3:3])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 6

HCID 311Citric AcidHCID 1032Propionic AcidHCID 6328Methyl iodideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 68890839[(S*)-2-(4-Benzyloxy-phenyl)-1-((S*)-5-oxo-2,5-dihydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl esterHCID 86605622Lithium bistrimethylsilylamide

生成物 1

HCID 11495571[(S*)-2-(3-Benzyloxy-phenyl)-1-((2S*,4R*)-4-methyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a solution of [(S*)-2-(4-Benzyloxy-phenyl)-1-((S*)-5-oxo-2,5-dihydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester (11.4 g, 27.7 mmol) in THF (35 ml) and DMPU (5 ml, 42 mmol, 1.5 eq) at −78° C. is added dropwise lithium-bis-(trimethylsilyl)-amide (55 ml 1M solution in THF, 55 mmol, 2 eq). After stirring at −78° C. for another 45 min methyliodide is added dropwise and the mixture is stirred another 3 h at −78° C. Propionic acid (10.3 ml, 138 mmol, 5 eq) is added followed by water (10 ml). After warming up to 0° C. a 10% solution of citric acid (72 ml) is added. The reaction mixture is extracted with EtOAc. The organic layer is washed with bicarbonate, 0.1N sodium sulfite and brine, dried over magnesium sulfate and evaporated. Purification by chromatography on silica (hexane/EtOAc 9/1 to 4/1) followed by recrystallization from ether/hexane gives white crystals (8.14 g).

後処理

  1. additionis added dropwise
  2. additionis added
  3. extractionThe reaction mixture is extracted with EtOAc
  4. washThe organic layer is washed with bicarbonate, 0.1N sodium sulfite and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customPurification by chromatography on silica (hexane/EtOAc 9/1 to 4/1)
  8. customfollowed by recrystallization from ether/hexane

出典と根拠

ORDレコード
ord-fd168027a4dd49a89b5072d425dc32a4
出典データセット
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07612054B2

反応ノート

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