Potassium Carbonate → {(1S,2S)-1-[5-(2-fluoro-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester

HRID 561979Notes

Reaction equation

HRID 561979 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][C:23]=2[F:29])=[CH:20][N:21]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2].O.C(O)C.C1(B(O)O)CC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:29])=[CH:20][N:21]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 19096565Water ethanolHCID 67001487{(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 67001749{(1S,2S)-1-[5-(2-fluoro-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl esterYield 107.1%

Reagents, catalysts & solvents 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a degassed mixture of {(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (150 mg, 0.288 mmol) in toluene (5 mL) and 1:1 v/v deionized water/ethanol (2 mL) were added dichlorobis(tricyclohexylphosphine)palladium(II) (6.4 mg, 0.009 mmol), cyclopropylboronic acid (27 mg, 0.314 mmol), potassium carbonate (159 mg, 1.15 mmol) and the mixture refluxed for 3 hours under an atmosphere of nitrogen. The mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The aqueous layer was washed with ethyl acetate (50 mL) and the combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted between 0 and 40% v/v ethyl acetate in hexanes to give {(1S,2S)-1-[5-(2-fluoro-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (122 mg, 107%) which was then used in step 17-G. HR-MS: calcd for C29H27FN4O4 [M+H+] 515.2089. Found 515.2089.

Workup

  1. temperaturethe mixture refluxed for 3 hours under an atmosphere of nitrogen
  2. washwashed with water (50 mL)
  3. washThe aqueous layer was washed with ethyl acetate (50 mL)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by chromatography over silica gel gradient
  9. washeluted between 0 and 40% v/v ethyl acetate in hexanes

Sources & evidence

ORD record
ord-638386412380420698f1d02379bb4263
Source dataset
uspto-grants-2011_11
Patent number
US08063085B2

Reaction notes

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