Glycolic Acid → (S)-Hydroxy-acetic acid 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indol-1-ylmethyl ester

HRID 585159Notes

Reaction equation

HRID 585159 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C@@:8]2([F:24])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[N:10]([CH2:21]Cl)[C:9]2=[O:23])[CH:7]=1.C(#N)C.[C:30]([OH:34])(=[O:33])[CH2:31][OH:32].C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C@@:8]2([F:24])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[N:10]([CH2:21][O:34][C:30](=[O:33])[CH2:31][OH:32])[C:9]2=[O:23])[CH:7]=1

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 86593818HCID 86593818, compound

Product 1

HCID 69329484(S)-Hydroxy-acetic acid 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indol-1-ylmethyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a 10 mL flask containing (S)-3-(5-chloro-2-methoxy-phenyl)-1-chloromethyl-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-V) (0.200 g, 0.489 mmol) was added 3 mL anhydrous acetonitrile, glycolic acid (0.045 g, 0.588 mmol) and cesium carbonate (0.079 g, 0.245 mmol). The reaction was stirred for 36 hours at room temperature, then the organic layer was diluted with 5 mL diethyl ether and the organic solution was decanted away from the solid cesium chloride. The solvent was evaporated in vacuo and the resulting white foam was purified by flash chromatography (silica gel 4:1 hexanes:acetone) producing the title compound (0.126 g, 58%) as a white powder. 1H NMR (CDCl3 400 MHz): δ=7.79 (s, 1H), 7.38-7.33 (m, 3H), 7.26 (d, 1H, J=7 Hz), 6.75 (d, 1H, J=7 Hz), 5.99 (d, 1H, J=12 Hz), 5.91 (d, 1H, J=12 Hz), 4.26 (s, 2H), 3.49 (s, 3H).

Workup

  1. customthe organic solution was decanted away from the solid cesium chloride
  2. customThe solvent was evaporated in vacuo
  3. customthe resulting white foam was purified by flash chromatography (silica gel 4:1 hexanes:acetone)

Sources & evidence

ORD record
ord-95d04a39228e4933989a30e32ba62f87
Source dataset
uspto-grants-2005_08
Patent number
US06930100B2

Reaction notes

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