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 585155Notes

Reaction equation

HRID 585155 reaction equation
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]

Participants

4

Reactant 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

Product 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 esterYield 57.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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%.

Workup

  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

Sources & evidence

ORD record
ord-446e448c14d34fd68a14a4a86d5e180f
Source dataset
uspto-grants-2005_08
Patent number
US06930100B2

Reaction notes

Loading…