N,O-Dimethylhydroxylamine → 4-Phenyl-5-propyl-thiophene-2-carboxylic acid methoxy-methyl-amide

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Reaction Steps

At −75° C., a solution of 4-phenylthiophene-2-carboxylic acid (1.20 g, 5.88 mmol) in THF (15 mL) is treated with tert.-BuLi (10 mL, 1.6 M in pentane). The mixture is stirred at −70° C. for 1 h before 1-iodopropane (1.5 mL) is added. The reaction mixture is allowed to warm to rt and is stirred overnight. The reaction is quenched with sat. aq. NH4Cl (100 mL) and extracted with DCM (2×200 mL). The solvent of the organic extracts is evaporated and the residue is dissolved in DCM (15 mL). TBTU (2.03 g, 6.33 mmol), N,O-dimethylhydroxylamine (760 mg, 7.80 mmol) and DIPEA (2 mL) is added and the mixture is stirred at rt for 72 h before it is washed with water. The organic layer is separated and evaporated. The residue is purified by CC on silica gel eluting with heptane:EA 5:1 to give 4-phenyl-5-propyl-thiophene-2-carboxylic acid methoxy-methyl-amide (900 mg) as colourless oil; LC-MS: tR=1.05 min, [M+1]+=290.15.

Provenance & Evidence