Citric Acid → (3-Chloro-4-cyano-2-methylphenyl)-D-threonine

HRID 470733

반응식

HRID 470733 반응식
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:12][C@@H:13]([C:17]([OH:19])=[O:18])[C@H:14]([CH3:16])[OH:15].C([O-])([O-])=O.[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([NH:12][C@H:13]([C@@H:14]([OH:15])[CH3:16])[C:17]([OH:19])=[O:18])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 69435D-ThreonineHCID 445509712-Chloro-4-fluoro-3-methylbenzonitrile

생성물 1

HCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
75 °C

실험 절차

2-chloro-4-fluoro-3-methylbenzonitrile (CAS 796600-15-2, 45 g, 265.4 mmol) was mixed together with H-D-Thr-OH (37.92 g, 318.4 mmol) in DMSO (250 mL). K2CO3 (73.35 g, 530.7 mmol) was added to the reaction mixture and the reaction mixture 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 on silica gel with a gradient of hexanes/EtOAc and then with EtOAc, 100% to get the purified final product (39.0 g, 54%) 1H NMR (500 MHz, Acetone-d6, δ in ppm) 7.49 (d, 9 Hz, 1H), 6.70 (d, J=9 Hz, 1H), 5.38 (d, J=10 Hz, 1H), 4.47 (d, J=6 Hz, 1H), 4.25 (m, 1H), 2.34 (s, 3H), 1.33 (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 on silica gel with a gradient of hexanes/EtOAc
  6. customwith EtOAc, 100% to get the
  7. custompurified final product (39.0 g, 54%) 1H NMR (500 MHz, Acetone-d6, δ in ppm) 7.49 (d, 9 Hz, 1H), 6.70 (d, J=9 Hz, 1H), 5.38 (d, J=10 Hz, 1H), 4.47 (d, J=6 Hz, 1H), 4.25 (m, 1H), 2.34 (s, 3H), 1.33 (d, J=6 Hz, 3H)

출처 및 근거

ORD 기록
ord-0996d674fb3d4ce791bf780f0a387e78
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629167B2

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