Cesium carbonate → HCID 68699922, compound

HRID 1990817Notes

Reaction equation

HRID 1990817 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([O:11][CH2:12][CH3:13])[CH:5]=1.[F:15][C:16]([F:20])([F:19])[CH2:17]I.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([O:10][CH2:17][C:16]([F:20])([F:19])[F:15])[CH:7]=[C:6]([O:11][CH2:12][CH3:13])[CH:5]=1

Participants

4

Reactant 3

HCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 15788544Methyl 3-ethoxy-5-hydroxybenzoate

Product 1

HCID 68699922HCID 68699922, compoundYield 42%

Conditions

Temperature
130 °C

Procedure

A mixture of 3-ethoxy-5-hydroxy-benzoic acid methyl ester (1.5 g, 7.65 mmol, 1.0 equiv; prepared as described in WO 99/05123 A1, Astra Pharmaceuticals Ltd.), 2,2,2-trifluoroethyl iodide (2.25 mL, 4.82 g, 22.94 mmol, 3.0 equiv) and cesium carbonate (4.98 g, 15.29 mmol, 2.0 equiv) was heated to 130° C. under microwave irradiation for 20 min. The crude reaction mixture was filtered over Hyflo Super Cel and extracted with dichloromethane (3×50 mL). The combined organic phases were dried over MgSO4, the solvent removed by evaporation under reduced pressure and the crude material purified by flash column chromatography on silica eluting with a gradient of heptane/dichloromethane (1:1→0:1) yielding 0.89 g (42%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.35 (t, J=7.0 Hz, 3H), 3.84 (s, 3H), 4.00 (q, J=7.0 Hz, 2H), 4.30 (q, J=8.1 Hz, 2H), 6.62-6.63 (m, 1H), 7.10-7.11 (m, 1H), 7.19-7.21 (m, 1H). MS (ISP): 279.0 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. filtrationwas filtered over Hyflo Super Cel
  3. extractionextracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. customthe solvent removed by evaporation under reduced pressure
  6. customthe crude material purified by flash column chromatography on silica eluting with a gradient of heptane/dichloromethane (1:1→0:1)

Sources & evidence

ORD record
ord-fea9bde581e84dd1a48f522a208e135e
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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