Cesium carbonate → HCID 67486484, compound

HRID 1755185Notes

Reaction equation

HRID 1755185 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=2)[C:12](=[O:21])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([I:20])=[CH:16][CH:15]=2)=[CH:6][CH:5]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:36](I)[C:37]([CH3:40])([CH3:39])[CH3:38]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH:11]([C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:26][CH:27]=2)[C:12](=[O:21])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([I:20])=[CH:16][CH:15]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 67486301HCID 67486301, compound

Product 1

HCID 67486484HCID 67486484, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-[2-(4-hydroxy-phenyl)-2-(4-iodo-phenyl-carbamoyl)-ethyl]-benzoic acid methyl ester (Step D, 0.6 g, 1.60 mmol) in DMF (15 mL) at rt were added Cs2CO3 (2.07 g, 6.38 mmol) and Neopentyliodide (2.53 g, 12.7 mmol). The reaction mixture was heated at 80° C. for 14 h and cool to rt and after completion of the reaction, the solvent was removed under reduced pressure and poured into H2O (50 mL). The aqueous solution was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was recrystallization in hexanes to afford 4-[2-(4-(2,2-dimethylpropoxy)-phenyl)-2-(4-iodo-phenyl-carbamoyl)-ethyl]-benzoic acid methyl ester as a yellow solid. (1.6 g, 88%): 1H NMR (300 MHz, CDCl3): δ 10.15 (s, 1H, NH), 7.80 (d, J=8.4 Hz, 2H), 7.53 (d, J=8.7 Hz, 2H), 7.35-7.26 (m, 6H), 6.82 (d, J=8.7 Hz, 2H), 3.93 (t, J=7.2 Hz, 1H), 3.77 (s, 3H), 3.54 (s, 2H), 3.35 (dd, J=9.0, 13.5 Hz, 1H), 2.98 (dd, J=6.6, 13.8 Hz, 1H), 0.94 (s, 9H); TLC conditions: Uniplate silica gel, 250 microns; mobile phase=ethyl acetate/hexanes (1:3); Rf=0.7.

Workup

  1. temperaturecool to rt
  2. customafter completion of the reaction
  3. customthe solvent was removed under reduced pressure
  4. additionpoured into H2O (50 mL)
  5. extractionThe aqueous solution was extracted with ethyl acetate (2×100 mL)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customrecrystallization in hexanes

Sources & evidence

ORD record
ord-eb5c1ac88462456b9ecaee10b60ddc7e
Source dataset
uspto-grants-2015_10
Patent number
US09169201B2

Reaction notes

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