ethyl 2-[(1R)-1-phenylethyl]iminoacetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (R)-1-phenyl-ethylamine (59 g, 0.49 mmol) dissolved in toluene (500 mL) was added sodium sulfate (173 g, 1.22 mmol) followed by oxo-acetic acid ethyl ester (134 g, 0.49 mmol, 50% in toluene) dropwise. The reaction mixture was stirred at RT for 1 h. The solid was filtered and the filtrate was concentrated under vacuum to provide ((R)-1-phenyl-ethylimino)-acetic acid ethyl ester, which was dissolved in DMF (300 mL) at RT. TFA (56 g, 0.49 mmol) was added dropwise at RT, followed after 10 min by cyclopenta-1,3-diene (65 g, 0.98 mmol) and water (0.25 ml). The mixture was stirred at RT overnight, concentrated under vacuum and the residue was poured into a 10% aqueous solution of NaHCO3 (500 mL). The solution was adjusted to pH 8 with solid Na2CO3, and extracted with EtOAc (3×80 mL). The combined organic layers were purified by silica gel chromatography (30:1-15:1 petroleum ether:EtOAc) to provide the title intermediate (35 g, 26% yield), as a colorless oil. (m/z): [M+H]+ calcd for C17H21NO2 272.16 found 272.2. The solid was filtered the filtrate was concentrated under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (R)-1-phenyl-ethylamine (59 g, 0.49 mmol) dissolved in toluene (500 mL) was added sodium sulfate (173 g, 1.22 mmol) followed by oxo-acetic acid ethyl ester (134 g, 0.49 mmol, 50% in toluene) dropwise. The reaction mixture was stirred at RT for 1 h. The solid was filtered and the filtrate was concentrated under vacuum to provide ((R)-1-phenyl-ethylimino)-acetic acid ethyl ester, which was dissolved in DMF (300 mL) at RT. TFA (56 g, 0.49 mmol) was added dropwise at RT, followed after 10 min by cyclopenta-1,3-diene (65 g, 0.98 mmol) and water (0.25 ml). The mixture was stirred at RT overnight, concentrated under vacuum and the residue was poured into a 10% aqueous solution of NaHCO3 (500 mL). The solution was adjusted to pH 8 with solid Na2CO3, and extracted with EtOAc (3×80 mL). The combined organic layers were purified by silica gel chromatography (30:1-15:1 petroleum ether:EtOAc) to provide the title intermediate (35 g, 26% yield), as a colorless oil. (m/z): [M+H]+ calcd for C17H21NO2 272.16 found 272.2. The solid was filtered the filtrate was concentrated under vacuum