Diisopropylamine → ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoate

HRID 1173617ノート

反応式

HRID 1173617 の反応式
C(NC(C)C)(C)C.[C:8]([O:11][CH2:12][CH3:13])(=[O:10])[CH3:9].[CH2:14]([O:21][C:22](=[O:34])[NH:23][C@H:24]([C:27](N1C=CN=C1)=[O:28])[CH2:25][CH3:26])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(OC(N[C@@H](CC)C(O)=O)=O)C1C=CC=CC=1>O1CCCC1.O.C(O)(=O)C>[CH2:14]([O:21][C:22]([NH:23][C@@H:24]([CH2:25][CH3:26])[C:27](=[O:28])[CH2:9][C:8]([O:11][CH2:12][CH3:13])=[O:10])=[O:34])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

参加物

8

反応物 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 7349998(2S)-2-(((Phenylmethoxy)carbonyl)amino)butanoic acidHCID 86652877benzyl[(1S)-1-(1H-imidazol-1-ylcarbonyl)propyl]carbamate

生成物 1

HCID 67105603ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoate収率 57%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of diisopropylamine (74.5 mL) in tetrahydrofuran (1 L) was cooled to −78° C., n-butyllithium-hexane solution (329 mL, 1.6 mol/L) was added dropwise, and the mixture was stirred for 1 hr. Ethyl acetate (51.6 mL) was added dropwise and the mixture was stirred at −78° C. for 1 hr. Then, a solution of benzyl[(1S)-1-(1H-imidazol-1-ylcarbonyl)propyl]carbamate prepared from (2S)-2-{[(benzyloxy)carbonyl]amino}butanoic acid (50 g) and N,N′-carbonyldiimidazole (39.5 g) in tetrahydrofuran (300 mL) was added dropwise at −78° C. After stirring at −78° C. for 1 hr, acetic acid was added to the reaction mixture. Water was added and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/0→2/1) to give ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoate as a colorless oil (yield: 36.7 g, 57%).

後処理

  1. additionn-butyllithium-hexane solution (329 mL, 1.6 mol/L) was added dropwise
  2. stirringthe mixture was stirred at −78° C. for 1 hr
  3. additionwas added dropwise at −78° C
  4. stirringAfter stirring at −78° C. for 1 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe extract was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/0→2/1)

出典と根拠

ORDレコード
ord-3db580d0e283458d95fd2b1217922ab8
出典データセット
uspto-grants-2010_11
特許番号
US07834051B2

反応ノート

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