Citric Acid → (4S)-5-(tert-Butoxy)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-oxopentanoic acid

HRID 530142노트

반응식

HRID 530142 반응식
[NH2:1][C@H:2]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[C:21](Cl)([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22].Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1.O>[CH:36]1[C:37]2[CH:25]([CH2:24][O:23][C:21]([NH:1][C@H:2]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6])=[O:22])[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:32]=2[CH:33]=[CH:34][CH:35]=1

참가 물질

8

반응물 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 1175051-(1,1-Dimethylethyl) hydrogen L-glutamate

생성물 1

HCID 7017912(4S)-5-(tert-Butoxy)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-oxopentanoic acid수율 99%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

To (S)-4-amino-5-tert-butoxy-5-oxopentanoic acid (1.50 g, 7.38 mmol) in 1,4-dioxane (40 mL) chilled to 0° C., sodium carbonate (196 mg, 1.85 mmol) in water (20 mL) was added followed by Fmoc chloride (2.11 g, 8.16 mmol). The reaction was gradually warmed to ambient temperature and stirred at ambient temperature for 16 hours. After this time, the reaction was made slightly acidic (pH=6) with 2 M hydrochloric acid and the pH adjusted to ˜3 with 1 M citric acid (˜80 mL). The resulting mixture was extracted with ethyl acetate (3×100 mL). The combined organics were dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography eluting with hexanes to a 3:2 ethyl acetate/hexane mixture to afford (S)-4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-tert-butoxy-5-oxopentanoic acid (3.10 g, 99%) as a white solid: 1H NMR (300 MHz, CDCl3) δ carboxylic acid peak (1H) not observed as it was too broadened out, 7.76 (d, J=7.5 Hz, 2H), 7.61-7.58 (m, 2H), 7.42-7.26 (m, 4H), 5.45 (d, J=7.8 Hz, 1H), 4.48-4.19 (m, 4H), 2.51-2.34 (m, 2H), 2.28-2.14 (m, 1H), 1.99-1.88 (m, 1H), 1.47 (s, 9H); ESI MS m/z=448 [M+Na]+.

후처리

  1. extractionThe resulting mixture was extracted with ethyl acetate (3×100 mL)
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue obtained
  6. customwas purified by silica gel column chromatography
  7. washeluting with hexanes to a 3:2 ethyl acetate/hexane mixture

출처 및 근거

ORD 기록
ord-1b6e911485a64e70ac4387294aefcbf1
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09352049B2

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