Ammonium Chloride → (2S,5R)-2-(3-bromo-5-fluorobenzyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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Reaction Conditions

Reaction Steps

To (R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (2 mL, 11.03 mmol) in THF (90 mL) at −78° C. was added n-BuLi (1.6 M in hexanes solution, 7.5 mL, 12 mmol). After stirring for 30 min, 1-bromo-3-(bromomethyl)-5-fluorobenzene (2.68 g, 10 mmol) in THF (10 mL) was added dropwise over 30 min. The temperature was maintained at −78° C. for 30 min then allowed to warm to ambient temperature. After stirring for 16 h, saturated aqueous NH4Cl (30 mL) was added followed by dilution with EtOAc and H2O. The THF was removed in vacuo and the remaining organics were separated and dried over sodium sulfate. After removal of solvent, the crude product was purified by silica gel chromatography to provide (2S,5R)-2-(3-bromo-5-fluorobenzyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (3.17 g, 77%). MS (m/z) 371 [M+H]+.

Provenance & Evidence