Methyl iodide → {1-[4-(4-Methoxyimino-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037322Notes

Reaction equation

HRID 1037322 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[N:28][OH:29])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:37](=O)([O-])[O-].[K+].[K+].IC.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[N:28][O:29][CH3:37])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 86671047(1-[4-(4-Hydroxyimino-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl)-carbamic acid tert-butyl ester

Product 1

HCID 86671048{1-[4-(4-Methoxyimino-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 90.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of {1-[4-(4-hydroxyimino-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (27 mg, 0.056 mmol) in DMF (2 mL) was added potassium carbonate (15.5 mg, 0.112 mmol) and iodomethane (0.011 mL, 0.168 mmol) at RT. After 2 hours, cesium carbonate (36.5 mg, 0.112 mmol) and iodomethane (0.021 mL, 0.336 mmol) were added and the mixture stirred for a further 1.5 hours. The reaction mixture was partitioned between EtOAc and water. The aqueous phase was isolated and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 25% EtOAc in cyclohexane) to afford the title compound (25.1 mg, 90%) as a colourless gum. LCMS (Method A): RT=5.20 min, [M+H]+=497.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. customThe aqueous phase was isolated
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5796c6df302044088c66db36ec9ca39f
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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