Dimethylformamide → HCID 86666715, compound

HRID 2401346Notes

Reaction equation

HRID 2401346 reaction equation
CS(O[CH2:6][C:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18](=[O:26])[C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[C:10]([CH3:27])[O:9][N:8]=1)(=O)=O.CN(C=O)C.[N-:33]=[N+:34]=[N-:35].[Na+]>O>[N:33]([CH2:6][C:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:26])=[C:10]([CH3:27])[O:9][N:8]=1)=[N+:34]=[N-:35]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 33557Sodium AzideHCID 86666716HCID 86666716, compound

Product 1

HCID 86666715HCID 86666715, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a round bottomed flask was added (4-chlorophenyl)(2-(3-(hydroxymethyl)-5-methylisoxazol-4-yl)phenyl)methanone (47.2 mg, 0.144 mmol), DCM, and Et3N (40.1 μl, 0.288 mmol). The solution was cooled to 0° C. before addition of Ms-Cl (13.47 μl, 0.173 mmol). The reaction was stirred at 0° C. for 30 min before addition of water. The layers were separated and the aqueous was extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated to afford crude (4-(2-(4-chlorobenzoyl)phenyl)-5-methylisoxazol-3-yl)methyl methanesulfonate. To a round bottomed flask was added (4-(2-(4-chlorobenzoyl)phenyl)-5-methylisoxazol-3-yl)methyl methanesulfonate (58.4 mg, 0.144 mmol), DMF, and sodium azide (28.1 mg, 0.432 mmol). The reaction was stirred at room temperature for 2 h before diluting with water and extracting the aqueous with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated to afford crude (2-(3-(azidomethyl)-5-methylisoxazol-4-yl)phenyl) (4-chlorophenyl)methanone. To a round bottomed flask was added (2-(3-(azidomethyl)-5-methylisoxazol-4-yl)phenyl)(4-chlorophenyl)methanone (50.8 mg, 0.144 mmol), toluene (3 mL), and trimethylphosphine solution (216 μl, 1M in toluene, 0.216 mmol). The reaction was stirred at room temperature over 2 days before purifying via Biotage (EtOAc/hex) to afford 6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,3-e]azepine. LC/MS m/z 309 [M+H]+; 1H NMR (400 MHz, Acetone) δ 7.70-7.76 (m, 1H), 7.63-7.70 (m, 1H), 7.32-7.49 (m, 6H), 5.10 (br. s, 1H), 4.10 (br. s, 1H), 2.68 (s, 3H).

Workup

  1. extractionextracting the aqueous with EtOAc
  2. washThe combined organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ea7435781e5f40a79dcd0eb1c4b18c80
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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