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Diphenylphosphinic chloride → tert-butyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-fluorobenzoate

HRID 1807313
ノート
印刷プレビュー

反応式

HRID 1807313 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.[NH2:63][C:64]1[CH:76]=[CH:75][C:67]([C:68]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:69])=[C:66]([F:77])[CH:65]=1>C(Cl)Cl>[C:71]([O:70][C:68](=[O:69])[C:67]1[CH:75]=[CH:76][C:64]([NH:63][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])([CH3:32])[CH3:34])[NH:17]2)=[O:36])=[CH:65][C:66]=1[F:77])([CH3:74])([CH3:72])[CH3:73]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 10058989Tert-butyl 4-amino-2-fluorobenzoateHCID 86642695CID 86642695

生成物 1

HCID 45137136tert-butyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-fluorobenzoate

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 (4.5 ml) to give a yellow 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 20 minutes. Tert-butyl 4-amino-2-fluorobenzoate (72.7 mg, 344 μmol, Eq: 1.00) was added and the reaction mixture was stirred at RT overnight. The crude reaction mixture was concentrated under vacuum. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 20% EtOAc in hexanes) to give a white solid as the product. 215 mg. MS (ES+) m/z Calcd: [(M+H)+]: 660, fund: 660.

後処理

  1. customto give a yellow solution
  2. stirringthe reaction mixture was stirred at RT overnight
  3. customThe crude reaction mixture
  4. concentrationwas concentrated under vacuum
  5. customThe crude material was purified by flash chromatography (silica gel, 40 g, 10% to 20% EtOAc in hexanes)
  6. customto give a white solid as the product

出典と根拠

ORDレコード
ord-97cfb664b16245328d2d9090f791059f
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08354444B2

反応ノート

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