4-Methylmorpholine → Ethyl 2-(2-((tert-butoxycarbonyl)amino)propanamido)-3-oxobutanoate

HRID 1930111ノート

反応式

HRID 1930111 の反応式
CN1CCOCC1.[C:8]([O:12][C:13]([NH:15][CH:16]([CH3:20])[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:40][CH:41]([C:47](=[O:49])[CH3:48])[C:42]([O:44][CH2:45][CH3:46])=[O:43]>C1COCC1>[C:8]([O:12][C:13]([NH:15][CH:16]([CH3:20])[C:17]([NH:40][CH:41]([C:47](=[O:49])[CH3:48])[C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:19])=[O:14])([CH3:9])([CH3:10])[CH3:11]

参加物

6

反応物 4

HCID 79724-Methylmorpholine2 回HCID 62365Isobutyl chloroformateHCID 2684712-N-Boc-aminopropionic acidHCID 86636663Butanoic acid, 2-amino-3-oxo-, ethyl ester, 4-methylbenzenesulfonate (1:1)

生成物 1

HCID 57992159Ethyl 2-(2-((tert-butoxycarbonyl)amino)propanamido)-3-oxobutanoate収率 68.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-25 °C

実験手順

A solution of 4-methylmorpholine (900 g) in THF (15 L) was added to 2-(tert-butoxycarbonylamino)propanoic acid (1690 g, 8933.17 mmol). The mixture was cooled to −25° C. and isobutyl chloroformate (1.164 L, 8933.17 mmol) was added. After 20 minutes the second equivalent of 4-methylmorpholine (900 g) was added followed by ethyl 2-amino-3-oxobutanoate Tosylate salt (see J-P. Genet et al, Eur. J. Org. Chem., 2004, 3017-3026) (2700 g, 8507.78 mmol) suspended in THF (2.5 L). The mixture was stirred at −25° C. for 30 minutes and then left to warm to ambient temperature overnight. The reaction was quenched with water (15 L), extracted with EtOAc (3×5 L) and the combined extracts washed with 50% saturated brine (5 L). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 2-(2-(tert-butoxycarbonylamino)propanamido)-3-oxobutanoate (1850 g, 68.7%).

後処理

  1. waitleft
  2. temperatureto warm to ambient temperature overnight
  3. customThe reaction was quenched with water (15 L)
  4. extractionextracted with EtOAc (3×5 L)
  5. washthe combined extracts washed with 50% saturated brine (5 L)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane
  11. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-ec8584dd9c77493fbd3557fc79beef21
出典データセット
uspto-grants-2012_05
特許番号
US08188092B2

反応ノート

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