Benzylamine → HCID 11098439, compound

Participants

Reaction Steps

Sources of Starting Materials as illustrated in FIG. 10, SCHEME B: α,β-Unsaturated amides with exocyclic double bonds: Reaction conditions: (a) TfOH, CHCl3, RT; (b) BnNH2, CHCl3, reflux; (c) 10 mol % Pd(PPh3)4, Bu3N, CO (1 atm), CH3CN, 65° C. Typical experimental procedure for the preparation of 700—described for the case in which n=1, X=Br, and R=Bn: Triflic acid (2.32 mL, 26.23 mmol) was added dropwise under N2 over 10 min to a stirred solution of propargyl bromide (2.0 mL, 26.23 mmol) in CHCl3 (30 mL) at 0° C. The ice bath was removed and the dark solution was stirred at RT for 60 min, followed by the addition of pyridine (5 mL). The solution was washed with water (50 mL) and dil. hydrochloric acid (2×50 mL). The organic phase was dried and the solvent evaporated. The residue was purified by Kugelrohr distillation to yield 1-bromo-2-[(trifluoromethanesulfonyl]oxylprop-2-ene as a colorless liquid. A solution of benzylamine (81 mL, 0.74 mmol) in CHCl3 (4 mL) was added dropwise to a mixture of 1-bromo-2-[(trifluoromethanesulfonyl)oxy]prop-2-ene (0.37 mmol) and Et3N (0.1 mL, 0.74 mmol) in CHCl3 (4 mL) at 1° C. The solution was then heated at reflux for 15 h. The mixture was washed with water (10 mL), the organic extracts were dried and the solvent was evaporated. The residue was purified by flash chromatography (hexanes-EtOAc, 9:1) to yield N-benzyl-2-[(trifluoromethanesulfonyl)oxy]-2-propenylamine as a pale yellow solid. Yield: 55%. Next, for the case in which n=1 and R=Bn: Carbon monoxide was bubbled through a solution of N-benzyl-2-[(trifluoromethanesulfonyl)oxy]-2-propenylamine (0.36 mmol), Pd(PPh3)4 (0.041 g, 0.036 mmol), tri-n-butylamine (0.17 mL, 0.72 mmol) in acetonitrile (15 mL) for 25 min. The reaction was then heated to 65° C. for 5 h. The solution was then allowed to cool to room temperature upon which ether (15 mL) was added and the solution filtered through a pad of kenite. The pad was subsequently thoroughly rinsed with ether (3×10 mL). The solvent was then removed in vaccuo and the residue taken up in dichloromethane. Flash chromatography (hexanes:ethyl acetate; 19:1) twice yielded 1-benzyl-3-methyleneazetidinone as a white amorphous solid. Yield: 73%.

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