Cesium carbonate → 5-Ethyl-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-4-trifluoromethyl-benzoic acid methyl ester

HRID 507051Notes

Reaction equation

HRID 507051 reaction equation
[CH3:1][O:2][C:3](=[O:8])[CH2:4][CH2:5][CH2:6]Br.[CH3:9][O:10][C:11](=[O:31])[C:12]1[CH:17]=[C:16]([CH2:18][CH3:19])[C:15]([C:20]([F:23])([F:22])[F:21])=[CH:14][C:13]=1[NH:24][C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:9][O:10][C:11](=[O:31])[C:12]1[CH:17]=[C:16]([CH2:18][CH3:19])[C:15]([C:20]([F:23])([F:22])[F:21])=[CH:14][C:13]=1[N:24]([C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26])[CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:8]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 107604Methyl 4-bromobutyrateHCID 594322985-Ethyl-2-isopropoxycarbonylamino-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 594325265-Ethyl-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-4-trifluoromethyl-benzoic acid methyl esterYield 78.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Add 4-bromo-butyric acid methyl ester (74.30 g, 410.46 mmol) to a mixture of 5-ethyl-2-isopropoxycarbonylamino-4-trifluoromethyl-benzoic acid methyl ester (39.05 g, 117.16 mmol) and cesium carbonate (114.65 g, 351.88 mmol) in N,N-dimethylformamide (800 mL). Heat the mixture at 90° C. for 4 h and the allow it to cool to room temperature. Filter the mixture through Celite then dilute the mixture with water (2 L) and ethyl acetate (2 L). Wash the organic layer with water (500 mL) and brine (500 mL). Dry the organic layer over anhydrous sodium sulfate and filter. Remove the solvents under reduced pressure and purify the resulting residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0 to 15%), to provide the title compound as a white solid (39.75 g, 78%): TLC Rf 0.42 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.0-1.10 (m, 3H), 1.22-1.32 (m, 6H), 1.78-1.89 (m, 2H), 2.37-2.40 (m, 2H), 2.82-2.89 (m, 2H), 3.41-3.80 (m, 5H), 3.89 (s, 3H), 4.78-5.02 (m, 1H), 7.43 (s, 1H), 7.91 (s, 1H).

Workup

  1. temperatureto cool to room temperature
  2. filtrationFilter the mixture through Celite
  3. additionthen dilute the mixture with water (2 L) and ethyl acetate (2 L)
  4. washWash the organic layer with water (500 mL) and brine (500 mL)
  5. dry with materialDry the organic layer over anhydrous sodium sulfate
  6. filtrationfilter
  7. customRemove the solvents under reduced pressure
  8. custompurify the resulting residue by column chromatography on silica gel
  9. washeluting with ethyl acetate/hexanes (0 to 15%)

Sources & evidence

ORD record
ord-d384613c645b484cb3a4f325dbf20b2d
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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