Trimethylphosphine → HCID 67951267, compound

HRID 2401347Notes

Reaction equation

HRID 2401347 reaction equation
[N:1]([CH2:4][C:5]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=O)=[C:8]([CH3:25])[O:7][N:6]=1)=[N+]=[N-].CP(C)C>C1(C)C=CC=CC=1>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9]3=[C:8]([CH3:25])[O:7][N:6]=[C:5]3[CH2:4][N:1]=2)=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 68983TrimethylphosphineHCID 86666715HCID 86666715, compound

Product 1

HCID 67951267HCID 67951267, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

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. custombefore purifying via Biotage (EtOAc/hex)

Sources & evidence

ORD record
ord-5015602ab04445fcbf18cd914664ba03
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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