Potassium Carbonate → 2-{5-[4-(5-Trifluoromethanesulfonyloxy-naphthalen-1-yl)-phenyl]-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71838Notes

Reaction equation

HRID 71838 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21](B3OC(C)(C)C(C)(C)O3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:33][C:34]([F:58])([F:57])[S:35]([O:38][C:39]1[CH:48]=[CH:47][CH:46]=[C:45]2[C:40]=1[CH:41]=[CH:42][CH:43]=[C:44]2OS(C(F)(F)F)(=O)=O)(=[O:37])=[O:36].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:19]=[CH:20][C:21]([C:44]3[C:45]4[C:40](=[C:39]([O:38][S:35]([C:34]([F:58])([F:33])[F:57])(=[O:36])=[O:37])[CH:48]=[CH:47][CH:46]=4)[CH:41]=[CH:42][CH:43]=3)=[CH:22][CH:23]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 149765711,5-Naphthalenebis(trifluoromethanesulfonate)HCID 574497592-{4-[4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-1h-imidazol-2-yl}pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 723380252-{5-[4-(5-Trifluoromethanesulfonyloxy-naphthalen-1-yl)-phenyl]-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 80.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.30 g, 2.96 mmol), Trifluoro-methanesulfonic acid 5-trifluoromethanesulfonyloxy-naphthalen-1-yl ester (982 mg, 2.31 mmol), Pd(PPh3)4 (134 mg, 0.116 mmol) and potassium carbonate (639 mg, 4.62 mmol) were suspended in toluene. After degassing with nitrogen for 28 min, the stirred suspension was heated to 100° C. for 18 hours. The reaction mixture was then cooled to RT, diluted with ethyl acetate (250 mL), washed with water, brine, dried over magnesium sulfate and concentrated. The resulting residue was purified by silica column chromatography (0% to 60% EtOAc/hexanes) to provide 2-{5-[4-(5-Trifluoromethanesulfonyloxy-naphthalen-1-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.09 g, 80%).

Workup

  1. customAfter degassing with nitrogen for 28 min
  2. temperatureThe reaction mixture was then cooled to RT
  3. additiondiluted with ethyl acetate (250 mL)
  4. washwashed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica column chromatography (0% to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ba0585b4d4a74e1885a85ffcb5fb209f
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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