Cesium carbonate → 3-[5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]-2,2,3-trifluoropropanoic acid

HRID 423371Notes

Reaction equation

HRID 423371 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[NH:22][CH:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH:33]([F:40])[C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([CH:33]([F:40])[C:34]([F:39])([F:38])[C:35]([OH:37])=[O:36])[CH:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 447173933-Bromo-2,2,3-trifluoropropanoic acidHCID 593183535-(3-Chloro-4-isopropoxyphenyl)-3-(1H-indol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 249870963-[5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]-2,2,3-trifluoropropanoic acidYield 4.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

D5 (200 mg), Cs2CO3 (552 mg) and DMF (2.8 ml) were stirred at RT and treated with 3-bromo-2,2,3-trifluoropropanoic acid (175 mg). This mixture was heated at 140° C. for 1 hour in a microwave reactor. 2 further equivalents of Cs2CO3 (368 mg) were added and heating continued at 140° C. for 10 hours. The reaction mixture was then evaporated, treated with H2O, shaken and filtered to give a brown solid residue. This was purified by MDAP to give the title compound (12 mg) as a white solid. δH (methanol-d4, 400 MHz): 1.42 (6H, d), 4.83 (1H, septet), 6.87 (1H, d), 7.29 (1H, d), 7.45 (1H, d), 7.54 (1H, d), 7.61 (1H, d), 7.80 (1H, d), 8.06 (1H, d), 8.11 (1H, d), 8.19-8.22 (1H, m), 8.44 (1H, s).

Workup

  1. temperatureheating
  2. customThe reaction mixture was then evaporated
  3. additiontreated with H2O
  4. filtrationfiltered
  5. customto give a brown solid residue
  6. customThis was purified by MDAP

Sources & evidence

ORD record
ord-09eb8233e5d74d238256d9dc0236cf4d
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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