Citric Acid → (2R,3S)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoic acid

HRID 470755

反応式

HRID 470755 の反応式
[Cl:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:11][C@@H:12]([C:16]([OH:18])=[O:17])[C@H:13]([CH3:15])[OH:14].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[CH:9]=[C:8]([NH:11][C@H:12]([C@@H:13]([OH:14])[CH3:15])[C:16]([OH:18])=[O:17])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

参加物

6

反応物 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 69435D-ThreonineHCID 1090002-Chloro-4-fluorobenzonitrile

生成物 1

HCID 67006723(2R,3S)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoic acid収率 55%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
75 °C

実験手順

2-chloro-4-fluorobenzonitrile (60702-69-4) (2.0 g, 12.86 mmol) was mixed together with H-D-Thr-OH (1.84 g, 15.43 mmol) in DMSO (30 mL). K2CO3 (3.73 g, 27.0 mmol) was added to the reaction mixture and stirred at 75° C. for 24 h. The reaction mixture was cooled down 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 1.8 g): 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.51 (d, J=9 Hz, 1H), 6.95 (s, 1H), 6.82 (d, J=9 Hz, 1H), 5.17 (d, J=9 Hz, 1H), 4.42 (m, 1H), 4.22 (d, J=6 Hz, 1H), 2.34 (s, 3H), 1.28 (d, J=6 Hz, 3H).

後処理

  1. temperatureThe reaction mixture was cooled down 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

出典と根拠

ORDレコード
ord-88382b334e3f4ce2b33f635e6e76605b
出典データセット
uspto-grants-2014_01
特許番号
US08629167B2

関連ノート

読み込み中…