Potassium Carbonate → (1-{2-[4-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 71719Notes

Reaction equation

HRID 71719 reaction equation
[CH3:1][O:2][C:3](=[O:35])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][C:14](F)(F)[CH2:13][CH:12]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[C:30][Si](C)(C)C)=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C([O-])([O-])=O.[K+].[K+]>CO>[CH3:1][O:2][C:3](=[O:35])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[CH:30])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 66620676(1-{4,4-difluoro-2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 72338228(1-{2-[4-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To (1-{4,4-difluoro-2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (412 mg, 0.82 mmol) in MeOH (8 mL) was added K2CO3 (227 mg, 1.64 mmol). After stirring for 5 h, the reaction was filtered then concentrated. The residue was diluted with EtOAc then washed with H2O. The aqueous phase was back-extracted with EtOAc two times then the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude material was purified by silica gel chromatography (20-80% EtOAc-hexanes gradient) to afford (1-{2-[5-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (371 mg, 0.82 mmol, quantitative yield). LCMS-ESI+: calc'd for C22H25F2N4O3: 431.2 (M+H+). Found: 431.1 (M+H+).

Workup

  1. filtrationthe reaction was filtered
  2. concentrationthen concentrated
  3. additionThe residue was diluted with EtOAc
  4. washthen washed with H2O
  5. extractionThe aqueous phase was back-extracted with EtOAc two times
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel chromatography (20-80% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-b1a3426db3364f7cb2fe795b09763e71
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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