Trifluoroacetic acid → (S)-3-(5-Chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid 2-phosphonooxy-propyl ester

HRID 585155ノート

反応式

HRID 585155 の反応式
C([O:5][P:6]([O:39]C(C)(C)C)([O:8][CH:9]([CH3:38])[CH2:10][O:11][C:12]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([F:26])([F:25])[F:24])[CH:21]=2)[C@@:16]([C:28]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])([F:27])[C:15]1=[O:37])=[O:13])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[P:6]([O:8][CH:9]([CH3:38])[CH2:10][O:11][C:12]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([F:24])([F:25])[F:26])[CH:21]=2)[C@@:16]([C:28]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])([F:27])[C:15]1=[O:37])=[O:13])([OH:7])([OH:39])=[O:5]

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 69330300(S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid 2-(di-tert-butoxy-phosphoryloxy)-propyl ester

生成物 1

HCID 10196400(S)-3-(5-Chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid 2-phosphonooxy-propyl ester収率 57.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid 2-(di-tert-butoxy-phosphoryloxy)-propyl ester ((S)-VII, n=2) (540 mg, 0.82 mmol) in dichloromethane (30 mL) was stirred with trifluoroacetic acid (0.6 mL) at room temperature for 3 hours. LC-MS indicated the completion of the reaction. After removal of the solvent the residue was dissolved in methanol and the crude product was purified by prep. HPLC, affording the title compound 255 mg (57%) as white solid after lyophilization. 1H NMR (CDCl3, 500 MHz) δ 8.27 (s, 1H), 7.73 (d, 1H), 7.42 (d, 1H), 7.32 (d, 1H), 7.27 (d, 1H), 6.75 (d, 1H), 4.50 (b, 6H, containing some H2O as solvate), 4.54 (m, 2H), 4.17 (b, 2H), 3.49 (s, 3H), 2.1 (m, 2H); MS (m/e) 539.92 (M+−1); LC-MS, 542 (MH+, 98.5%); 31P NMR (CDCl3, 500 MHz) δ 2.03; 19F NMR (CDCl3, 500 MHz) δ−63.4, 153.8; Anal. Calcd. for C20H17ClF4NO8P: C=44.34%, H=3.16%, N=2.58%; Found: C=44.01%, H=3.11%, N=2.45%.

後処理

  1. customthe completion of the reaction
  2. customAfter removal of the solvent the residue
  3. dissolutionwas dissolved in methanol
  4. customthe crude product was purified by prep

出典と根拠

ORDレコード
ord-446e448c14d34fd68a14a4a86d5e180f
出典データセット
uspto-grants-2005_08
特許番号
US06930100B2

反応ノート

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