Toluene → HCID 57991962, compound

HRID 2075347Notes

Reaction equation

HRID 2075347 reaction equation
FC(F)(F)S(O[C:7]1[C@@H:8]([C:31]([O:33][CH3:34])=[O:32])[N:9]([C:12]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][CH:11]=1)(=O)=O.[F:37][C:38]([F:49])([F:48])[C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1.C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>CO>[F:37][C:38]([F:49])([F:48])[C:39]1[CH:44]=[CH:43][C:42]([C:7]2[C@@H:8]([C:31]([O:33][CH3:34])=[O:32])[N:9]([C:12]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:10][CH:11]=2)=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 11398226HCID 11398226, compound

Product 1

HCID 57991962HCID 57991962, compoundYield 62.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred mixture of (S)-methyl 3-(trifluoromethylsulfonyloxy)-1-trityl-2,5-dihydro-1H-pyrrole-2-carboxylate ((Tetrahedron Lett. 2001, 8571) 1.71 g, 3.3 mmol), 4-(trifluoromethyl)phenylboronic acid (1.3 g, 6.6 mmol), K2CO3 (0.68 mg, 5.0 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) DCM adduct (0.12 g, 0.16 mmol) was added toluene (10 mL) and MeOH (1.0 mL). The mixture was stirred under nitrogen at 85° C. 15 hours. The mixture was cooled and evaporated in vacuo. The residue was dissolved in DCM, adsorbed onto silica gel and purified by flash column chromatography (eluting first with 1:5 EtOAc in hexanes and second with a gradient of hexanes to 30% DCM in hexanes) to give (S)-methyl 3-(4-(trifluoromethyl)phenyl)-1-trityl-2,5-dihydro-1H-pyrrole-2-carboxylate as a white solid (1.06 g, 62%). LCMS (M+H) 514.5 calc. for C32H27F3NO2 514.2. 1H NMR (400 MHz, CDCl3): δ ppm 6.67-8.21 (a series of m, 19H) 5.85 (s, 1H) 5.01 (d, J=4.11 Hz, 1H) 4.39 (dd, J=17.61, 2.54 Hz, 1H) 3.82 (dd, J=17.70, 2.64 Hz, 1H) 3.64 (s, 3H).

Workup

  1. custom15 hours
  2. temperatureThe mixture was cooled
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in DCM
  5. custompurified by flash column chromatography (
  6. washeluting first with 1:5 EtOAc in hexanes and second with a gradient of hexanes to 30% DCM in hexanes)

Sources & evidence

ORD record
ord-b4c0084b3db645fc97d13addfa468c20
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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