Trifluoroacetic acid → VX-765

HRID 2220108ノート

反応式

HRID 2220108 の反応式
C([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13](=[O:30])[CH:14]([NH:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([Cl:28])[CH:22]=1)[C:15]([CH3:18])([CH3:17])[CH3:16])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]([NH:19][CH:14]([C:15]([CH3:16])([CH3:17])[CH3:18])[C:13]([N:9]2[CH2:10][CH2:11][CH2:12][CH:8]2[C:6]([OH:7])=[O:5])=[O:30])=[O:29])=[CH:22][C:23]=1[Cl:28]

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 102034841-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carboxylic acid tert-butyl ester

生成物 1

HCID 10156704VX-765収率 101%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 4 (15.9 g, 36.3 mmol) in CH2Cl2 (30 mL) was added TFA (trifluoroacetic acetic acid)(30 mL) and the solution stirred at room temperature for 3 hours under N2. The reaction was transfered to a beaker (1 L) and diluted with CH2Cl2 (60 mL). To the solution at 0° C. was added solid NaHCO3 (39 g, 46 mmol) and stirred for 15 minutes before partitioning between EtOAc (300 mL) and H2O (300 mL). After extraction the aqueous layer was acidified to pH 4–5 and extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated to dryness to give 5 as a white solid (14.0 g, quantitative yield): 1H-NMR (500 MHz, CDCl3) δ1.08 (s, 9H), 1.97–2.22 (m, 3H), 2.29–2.41 (m, 1H), 3.71–3.78 (m, 1H), 3.90–3.98 (m, 1H), 4.55–4.62 (m, 1H), 4.86 (d, 1H), 6.64 (d, 1H), 6.74 (d, 1H), 7.53 (d, 1H), 7.74 (s, 1H). Analytical HPLC (cyano column): 8.24 min. LC-MS (ES+) m/e=382.4 (M+H).

後処理

  1. stirringstirred for 15 minutes
  2. custombefore partitioning between EtOAc (300 mL) and H2O (300 mL)
  3. extractionAfter extraction the aqueous layer
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customevaporated to dryness

出典と根拠

ORDレコード
ord-f84e607d17734ddb98019306f102c0ae
出典データセット
uspto-grants-2008_08
特許番号
US07417029B2

反応ノート

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