p-Bromoacetophenone → HCID 59736672, compound

HRID 252824Notes

Reaction equation

HRID 252824 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:3]=1[NH:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1.Br[C:29]1[CH:34]=[CH:33][C:32]([C:35](=[O:37])[CH3:36])=[CH:31][CH:30]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:35]([C:32]1[CH:33]=[CH:34][C:29]([C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([NH:17][C:18](=[O:27])[C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[CH:4]=2)=[CH:30][CH:31]=1)(=[O:37])[CH3:36]

Participants

7

Reactant 4

HCID 7466p-BromoacetophenoneHCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 59736794HCID 59736794, compound

Product 1

HCID 59736672HCID 59736672, compoundYield 25.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

In a pressure vessel, N-[2-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-4-methoxybenzamide (116) (170 mg, 0.462 mmol), 1-(4-bromophenyl)ethanone (184 mg, 0.923 mmol), (or any aryl bromide from the tables below), DME (4.6 mL per mmol of 116) and H2O (2.15 mL per mmol of 116) were added. Air was then removed by vacuum and then the vessel was purged with nitrogen. Pd(PPh3)4 (27 mg, 0.023 mmol, 0.05 eq.) and Na2CO3 (147 mg, 1.38 mmol, 3.0 eq.) were then added and oxygen was removed after each addition. The pressure vessel was sealed and the mixture was stirred at 75° C. overnight. The mixture was cooled at room temp., water was added and the mixture was extracted with EtOAc. The combined organic layers were rinsed with brine, dried over MgSO4 and concentrated to give 42 mg (25%) of the title compound 117. 1H NMR (DMSO-d6) (ppm): 9.61 (s, 1H), 7.96 (dd, J=12.8, 8.8 Hz, 4H), 7.70 (d, J=8.8 Hz, 2H), 7.60 (d, J=2.1 Hz, 1H), 7.42 (dd, J=8.4, 2.3 Hz, 1H), 7.04 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.2 Hz, 1H), 5.26 (s, 2H), 3.84 (s, 3H), 2.58 (s, 3H). MS (m/z): 360.41 (calc) 361.1 (MH+) (found).

Workup

  1. customAir was then removed by vacuum
  2. customthe vessel was purged with nitrogen
  3. customoxygen was removed
  4. additionafter each addition
  5. customThe pressure vessel was sealed
  6. temperatureThe mixture was cooled at room temp.
  7. additionwater was added
  8. extractionthe mixture was extracted with EtOAc
  9. washThe combined organic layers were rinsed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-9ce452e3cb2e46edbc0202531e3bbd06
Source dataset
uspto-grants-2011_01
Patent number
US07868205B2

Reaction notes

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