Trifluoroacetic acid → HCID 53246384, compound

HRID 1189575Notes

Reaction equation

HRID 1189575 reaction equation
[CH3:1][C:2]1[N:3]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:5][C:6]=1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)(=[O:16])=[O:15].[C:35](O)([C:37]([F:40])([F:39])[F:38])=[O:36]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][C:2]1[N:3]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:4]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:5]([C:35](=[O:36])[C:37]([F:40])([F:39])[F:38])[C:6]=1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14]([N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1)(=[O:16])=[O:15]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58310940HCID 58310940, compound

Product 1

HCID 53246384HCID 53246384, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 2-(2-methyl-3-(2-(morpholinosulfonyl)benzyl)-5-phenyl-1H-pyrrol-1-yl)acetate (0.259 g, 0.537 mmol) (mixture of regioisomers—1.5:1.0) was dissolved in DCM (5.37 ml) and cooled to 0° C. DMAP (0.262 g, 2.147 mmol) was then added to the reaction in one portion, followed by TFA (0.758 ml, 5.37 mmol) in a drop-wise fashion. The ice bath was removed and the reaction was warmed to rt then refluxed for 16 h. At this time, the reaction was quenched with 1N HCl, and then diluted with 50 mL DCM. The layers were separated and the aqueous portion was then back-extracted with DCM (50 mL). The organics were combined, dried, filtered, and concentrated. The crude material ethyl 2-(2-methyl-3-(2-(morpholinosulfonyl)benzyl)-5-phenyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrol-1-yl)acetate was then purified by silica gel chromatography using a 0-70% EtOAc/hexane gradient to furnish the desired material in 67% yield.

Workup

  1. customThe ice bath was removed
  2. temperaturethe reaction was warmed to rt
  3. temperaturethen refluxed for 16 h
  4. customAt this time, the reaction was quenched with 1N HCl
  5. additiondiluted with 50 mL DCM
  6. customThe layers were separated
  7. extractionthe aqueous portion was then back-extracted with DCM (50 mL)
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material ethyl 2-(2-methyl-3-(2-(morpholinosulfonyl)benzyl)-5-phenyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrol-1-yl)acetate was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-43d193fa7640481f87c61882f4f67522
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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