Methyl Acrylate → methyl 4-(tert-butoxycarbonyl((S)-1-(tert-butyldimethylsilyloxy)but-3-en-2-yl)amino)-3-hydroxy-2-methylenebutanoate

HRID 627140

反応式

HRID 627140 の反応式
[Si:1]([O:8][CH2:9][C@@H:10]([N:13]([CH2:21][CH:22]=[O:23])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:11]=[CH2:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:24]([O:28][CH3:29])(=[O:27])[CH:25]=[CH2:26].N12CCC(CC1)CC2>O.CO.C(OCC)(=O)C>[C:16]([O:15][C:14]([N:13]([C@@H:10]([CH:11]=[CH2:12])[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[CH2:21][CH:22]([OH:23])[C:25](=[CH2:26])[C:24]([O:28][CH3:29])=[O:27])=[O:20])([CH3:19])([CH3:18])[CH3:17]

参加物

7

反応物 3

HCID 7294Methyl Acrylate2 回HCID 7527Quinuclidine2 回HCID 89863148(S)-tert-butyl 1-(tert-butyldimethylsilyloxy)but-3-en-2-yl(2-oxoethyl)carbamate2 回

生成物 1

HCID 89851332methyl 4-(tert-butoxycarbonyl((S)-1-(tert-butyldimethylsilyloxy)but-3-en-2-yl)amino)-3-hydroxy-2-methylenebutanoate収率 80%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)but-3-en-2-yl(2-oxoethyl)carbamate (Intermediate 99, 16.1 g, 46.8 mmol), methyl acrylate (6.3 mL, 70 mmol), and methanol (about 2 mL), under nitrogen at ambient temperature, was added Quinuclidine (2.1 g, 19 mmol) as a solid. The mixture was then stirred for 1 day; analysis by TLC (15% ethyl acetate in hexanes) indicated incomplete conversion of starting material. Another 0.8 eq of quinuclidine was added every 24 hours; another 0.75 eq methyl acrylate and 1 mL methanol were added every two days. After 6 days total, the reaction was diluted with water and extracted with ethyl acetate. TLC indicated that only one extraction with about 250 mL ethyl acetate was needed to bring all the crude product into the organic layer, which was then washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Normal-phase chromatography (5-30% ethyl acetate in hexanes, 220-g column, 35 minutes) afforded the desired compound (16 g, 80%, pale oil) as a mixture of diastereomers, with about 10 mol % of starting aldehyde present according to proton NMR analysis. The material was taken forward in this state.

後処理

  1. waitAfter 6 days total
  2. extractionextracted with ethyl acetate
  3. extractionTLC indicated that only one extraction with about 250 mL ethyl acetate
  4. washwas then washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-5d033dc43e3845008ed1fd1e3711fb17
出典データセット
uspto-grants-2016_04
特許番号
US09309245B2

関連ノート

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