Nitrogen → HCID 67814343, compound

HRID 2401335Notes

Reaction equation

HRID 2401335 reaction equation
C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)=[O:15].N#N.[C:25]([O:33][CH2:34][C:35]1[O:39][N:38]=[C:37]([CH3:40])[C:36]=1B1OC(C)(C)C(C)(C)O1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[C:25]([O:33][CH2:34][C:35]1[O:39][N:38]=[C:37]([CH3:40])[C:36]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14](=[O:15])[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)(=[O:32])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

9

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 15499651(2-Bromophenyl)(4-chlorophenyl)methanoneHCID 67817705HCID 67817705, compound

Product 1

HCID 67814343HCID 67814343, compound

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a resealable vial was added Pd(OAc)2 (3.87 mg, 0.017 mmol) and X-phos (16.42 mg, 0.034 mmol) before the vial was sealed and evacuated and purged with N2 (3×). To this vial was added (4-bromo-3-methylisoxazol-5-yl)methyl benzoate (102 mg, 0.344 mmol) in dioxane (1 mL), Et3N (144 μl, 1.033 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane solution (517 μl, 1M in THF, 0.517 mmol). The reaction was stirred overnight at 80° C., cooled to room temperature and filtered. The filtrate was concentrated to afford crude (3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)methyl benzoate. To a resealable vial was added K2CO3 (47.5 mg, 0.344 mmol), PdCl2(dppf)-CH2Cl2 Adduct (20.06 mg, 0.025 mmol), (2-bromophenyl)(4-chlorophenyl)methanone (72.6 mg, 0.246 mmol). The vial was sealed and evacuated and purged with N2 (3×) before addition of crude (3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)methyl benzoate (118 mg, 0.344 mmol) dissolved in dioxane (2 mL). Water (0.5 mL) was then added to this solution before the vial was heated to 110° C. overnight. The reaction was cooled to room temperature, diluted with EtOAc, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford (4-(2-(4-chlorobenzoyl)phenyl)-3-methylisoxazol-5-yl)methyl benzoate. LC/MS m/z 432 [M+H]+.

Workup

  1. customThe vial was sealed
  2. customevacuated
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified via Biotage (EtOAc/hex)

Sources & evidence

ORD record
ord-8befd9186f444b4b9dd6ef77ebf8b040
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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