Citric Acid → (2r,3s)-2-(4-Cyanonaphthalen-1-ylamino)-3-hydroxybutanoic acid

HRID 1254651

반응식

HRID 1254651 반응식
F[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]#[N:13])=[CH:4][CH:3]=1.[NH2:14][C@@H:15]([C:19]([OH:21])=[O:20])[C@H:16]([CH3:18])[OH:17].C([O-])([O-])=O.[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:12]([C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([NH:14][C@H:15]([C@@H:16]([OH:17])[CH3:18])[C:19]([OH:21])=[O:20])=[CH:3][CH:4]=1)#[N:13]

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 69435D-ThreonineHCID 27367341-Cyano-4-fluoronaphthalene

생성물 1

HCID 67006572(2r,3s)-2-(4-Cyanonaphthalen-1-ylamino)-3-hydroxybutanoic acid수율 69.7%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
75 °C

실험 절차

4-fluoro-1-naphthonitrile (13916-99-9) (1.0 g, 5.84 mmol) was mixed together with H-D-Thr-OH (835 mg, 7.01 mmol) in DMSO (20 mL). K2CO3 (1.61 g, 11.68 mmol) was added to the reaction mixture and stirred at 75° C. for 24 h. The reaction mixture was cooled to room temperature and poured slowly into a 10% citric acid solution and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times to get the crude product. The crude product was chromatographed with a gradient of hexane/EtOAc and then with EtOAc, 100% to get the pure final product (1.1 g): 1H NMR (500 MHz, acetone-d6, δ in ppm) 8.25 (d, J=9 Hz, 1H), 8.09 (d, J=9 Hz, 1H), 7.84 (d, J=9 Hz, 1H), 7.75 (t, J=9 Hz, 1H), 7.65 (t, J=9 Hz, 1H), 6.70 (d, J=9 Hz, 1H), 6.32 (d, J=9 Hz, 1H), 4.53 (m, 1H), 4.38 (m, 1H), 1.40 (d, J=6 Hz, 3H).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringstirred for 10 min at room temperature
  3. extractionThe solution was extracted with EtOAc several times
  4. customto get the crude product
  5. customThe crude product was chromatographed with a gradient of hexane/EtOAc

출처 및 근거

ORD 기록
ord-77fc68bd6d9a489b99eb3a404e810b03
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455525B2

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