L-Methionine → 2,4-Dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Participants

Reaction Steps

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine, (Preparation S, 3.56 g, 12.57 mmol) in DME (Volume: 84 mL) at −78° C. was added KHMDS (0.91 M in THF, 15.20 ml, 13.83 mmol) dropwise. After 10 min, Met (2.36 mL, 37.7 mmol) was added. The reaction was kept at −78° C. for 10 min, then allowed to come to rt. An aliquot taken while the reaction was still cool was quenched with water and extracted with EtOAc. TLC (10% EtOAc/Hex) and LC/MS showed the clean conversion to a new product. The bulk of the material was then quenched and extracted as above. The combined organic extracts were dried over MgSO4, filtered, and the solvent removed in vacuo. SG chromatography (0 to 40% EtOAc/Hex) gave 2,4-dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (3.01 g, 10.13 mmol, 81% yield). LC-MS (*M*+H)+=293.1 (*product reacts with methanol during analysis*). 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.29 (2H, m), 6.96-7.04 (2H, m), 2.88-3.02 (2H, m), 2.62 (1H, ddd, J=13.28, 7.93, 5.04 Hz), 2.26-2.35 (1H, m), 1.68 (3H, s).

Provenance & Evidence