Dichloromethane → tert-butyl (2S,4S)-4-methyl-2-[4-[4-(2-trimethylsilylethynyl)phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate

HRID 1625513Notes

Reaction equation

HRID 1625513 reaction equation
I[C:2]1[N:3]=[C:4]([C@@H:7]2[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[NH:5][CH:6]=1.[CH3:20][Si:21]([CH3:34])([CH3:33])[C:22]#[C:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C(Cl)Cl.C([O-])(O)=O.[Na+]>C(O)(C)C>[CH3:12][C@@H:10]1[CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:7]([C:4]2[NH:5][CH:6]=[C:2]([C:27]3[CH:28]=[CH:29][C:24]([C:23]#[C:22][Si:21]([CH3:20])([CH3:34])[CH3:33])=[CH:25][CH:26]=3)[N:3]=2)[CH2:11]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 46739765(4-((Trimethylsilyl)ethynyl)phenyl)boronic acidHCID 53261949(2S,4S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate

Product 1

HCID 178461452tert-butyl (2S,4S)-4-methyl-2-[4-[4-(2-trimethylsilylethynyl)phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylateYield 99.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of tert-butyl (2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (150 mg, 0.3976 mmol) and ([4-(2-trimethylsilylethynyl)phenyl]boronic acid (130 mg, 0.6 mmol) in isopropanol (3 mL) are added sequentially Pd(DPPF)(Cl)2.CH2Cl2 (16 mg, 0.02 mmol), and 2 M NaHCO3 (600 uL, 1.2 mmol). The mixture is heated to 85° C. in a sealed tube overnight. After reaction, the solvent is removed under reduced pressure and the residue is purified by flash column chromatography on silica gel using methanol/CH2Cl2 0-5% to provide tert-butyl (2S,4S)-4-methyl-2-[4-[4-(2-trimethylsilylethynyl)phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (168 mg, 95%).

Workup

  1. customAfter reaction
  2. customthe solvent is removed under reduced pressure
  3. customthe residue is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-a0a66c4a15d94124bdc0403d1038dc4b
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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