Citric Acid → (2S,4R)-1-(2-{[(benzyloxy)carbonyl]amino}acetyl)-4-hydroxypyrrolidine-2-carboxylic acid

HRID 250800

반응식

HRID 250800 반응식
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.C(=O)([O-])O.[Na+].ON1C(=O)CCC1=O.[C:23]([O:27][C:28]([NH:30][CH2:31][C:32]([OH:34])=O)=[O:29])([CH3:26])(C)C.[C:35](O)(=O)[CH2:36][C:37]([CH2:42][C:43](O)=O)(C(O)=O)O>O.O1CCOCC1>[CH2:23]([O:27][C:28]([NH:30][CH2:31][C:32]([N:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])=[O:34])=[O:29])[C:26]1[CH:43]=[CH:42][CH:37]=[CH:36][CH:35]=1

참가 물질

7

반응물 4

HCID 311Citric AcidHCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 22022511N-tert-butyloxycarbonylglycine N-hydroxysuccinimide

생성물 1

HCID 58088404(2S,4R)-1-(2-{[(benzyloxy)carbonyl]amino}acetyl)-4-hydroxypyrrolidine-2-carboxylic acid수율 100%

시약·촉매·용매 2

HCID 962Water용매2회HCID 312751,4-Dioxane용매

실험 절차

3,4-Dehydroproline 1 (0.011 g, 0.097 mmol) and sodium hydrogen carbonate (0.0082 g, 0.097 mmol) were dissolved in water (1 cm3). A solution of N-tert-butyloxycarbonylglycine N-hydroxysuccinimide 2 (0.024 g, 0.088 mmol) in dioxane (1 cm3) was added dropwise and stirred overnight. The reaction mixture was diluted with water, acidified with solid citric acid and extracted with dichloromethane (3×). The combined organic layers were dried (MgSO4), filtered and the solvent removed to afford crude acid 3 (0.0242 g, ca. 100%) that was used without further purification. Acid 3 was shown to be a 75:25 trans:cis mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the Proα protons at δ 5.21 and 5.13 of the major and minor conformers respectively): δH (300 MHz; CDCl3; Me4Si) 1.411 [2.25H, s, C(CH3)3], 1.42 [6.75H, s, C(CH3)3], 3.83-4.08 (2H, m, Glyα-H2), 4.25-4.45 (2H, m, Proδ-H2), 5.13* (0.25H, br d, J 2.8, Pros-H), 5.21 (0.75H, br d, J 3.1, Proα-H), 5.55-5.80 (2H, br m, O—H and N—H) and 5.86-6.02 (2H, m, Proβ-H and Proγ-H).

후처리

  1. extractionextracted with dichloromethane (3×)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent removed

출처 및 근거

ORD 기록
ord-91cfb877ddec4ee8a3ea2174fa2ecf2a
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863304B2

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