Diphenylphosphinic chloride → (2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-iodo-2-trifluoromethoxy-phenyl)-amide

HRID 1807316ノート

反応式

HRID 1807316 の反応式
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:38])=[C:11]([C@@H:15]2[C@:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[C@H:18]([CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[NH:17][C@H:16]2[C:35](O)=[O:36])[CH:12]=[CH:13][CH:14]=1.CCN(C(C)C)C(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[I:63][C:64]1[CH:70]=[CH:69][C:67]([NH2:68])=[C:66]([O:71][C:72]([F:75])([F:74])[F:73])[CH:65]=1>C(Cl)Cl>[I:63][C:64]1[CH:70]=[CH:69][C:67]([NH:68][C:35]([C@H:16]2[C@H:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=3[F:38])[C@:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[C@H:18]([CH2:30][C:31]([CH3:33])([CH3:34])[CH3:32])[NH:17]2)=[O:36])=[C:66]([O:71][C:72]([F:73])([F:74])[F:75])[CH:65]=1

参加物

6

反応物 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 27613984-Iodo-2-(trifluoromethoxy)anilineHCID 86642695CID 86642695

生成物 1

HCID 53358689(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-iodo-2-trifluoromethoxy-phenyl)-amide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a 25 mL round-bottomed flask, (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid compound with 2,2,2-trifluoroacetic acid (1:1) (200 mg, 344 μmol, Eq: 1.00), was combined with CH2Cl2 (5 ml) to give a clear solution. DIPEA (178 mg, 1.38 mmol, Eq: 4) and diphenylphosphinic chloride (244 mg, 1.03 mmol, Eq: 3) were added and the reaction was stirred at RT for 30 minutes. 4-Iodo-2-(trifluoromethoxy) aniline (136 mg, 447 μmol, Eq: 1.3) was added and the reaction mixture was stirred at RT overnight. The crude reaction mixture was concentrated in vacuum. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 20% EtOAc/Hexanes) to give the desired product as a white solid. 255 mg. (ES+) m/z Calcd: [(M+)+]: 752. found: 752.

後処理

  1. customto give a clear solution
  2. stirringthe reaction mixture was stirred at RT overnight
  3. customThe crude reaction mixture
  4. concentrationwas concentrated in vacuum
  5. customThe crude material was purified by flash chromatography (silica gel, 40 g, 0% to 20% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-e2efe0c21fa545c3a4097b5cfb7e5c3a
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

読み込み中…