3-bromo-2-phenyl-4H-chromen-4-one → {1-[4-(4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037267

Reaction equation

HRID 1037267 reaction equation
Br[C:2]1[C:7](=[O:8])[C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[O:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19]([O:23][C:24](=[O:45])[NH:25][C:26]1([C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)[CH2:29][CH2:28][CH2:27]1)([CH3:22])([CH3:21])[CH3:20]>C1(C)C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>[C:19]([O:23][C:24](=[O:45])[NH:25][C:26]1([C:30]2[CH:31]=[CH:32][C:33]([C:2]3[C:7](=[O:8])[C:6]4[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=4[O:4][C:3]=3[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:34][CH:35]=2)[CH2:27][CH2:28][CH2:29]1)([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 2

HCID 4662783-bromo-2-phenyl-4H-chromen-4-oneHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 67067804{1-[4-(4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a round-bottom flask was added 3-bromo-2-phenyl-1-benzopyran-4-one (27.1 mg, 0.09 mmol) and {1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (50.4 mg, 0.135 mmol) in toluene:ethanol (4:1, 2.5 mL) and 2 M aqueous sodium carbonate (1 mL). The solution was degassed for 20 minutes, after which time, tetrakis(triphenylphosphine) palladium (5.2 mg, 5 mol %) was added. The reaction mixture was heated to 80° C. using an oil bath with a water cooled reflux condenser, while stirring for 21 hours. The reaction mixture cooled to RT, suspended in ethyl acetate and washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (10:1 to 5:1 hexane:EtOAc gradient) to give a white solid (12.2 mg, 94%). 1H-NMR (400 MHz, CDCl3) δ 8.30 (d, 1H), 7.66 (dd, 1H), 7.53 (dd, 1H), 7.38-7.45 (m, 3H), 7.30-7.36 (m, 3H), 7.27 (d, 2H), 7.19 (d, 2H), 5.11 (bs, 1H), 2.35-2.58 (m, 4H), 1.91-2.09 (m, 1H), 1.77-1.88 (m, 1H), 1.38 (bs, 9H).

Workup

  1. customThe solution was degassed for 20 minutes
  2. additionafter which time, tetrakis(triphenylphosphine) palladium (5.2 mg, 5 mol %) was added
  3. temperaturecooled
  4. temperaturereflux condenser
  5. temperatureThe reaction mixture cooled to RT
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by silica gel chromatography (10:1 to 5:1 hexane:EtOAc gradient)

Sources & evidence

ORD record
ord-8399ac40b0c0400ea3c3bd211e065bbb
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Linked notes

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