Ammonium Chloride → HCID 70944694, compound

Participants

Reaction Conditions

Reaction Steps

To a THF (53 mL) solution of tert-butyl 4-(4-bromo-2-fluorobenzyl)piperazine-1-carboxylate (5.331 g) was added slowly n-BuLi (11.48 mL, 2.6 M in hexane) at −78° C., then the resultant mixture was stirred for 0.5 hour. To the mixture was added slowly DMF (1.681 mL) at −78° C., then the resultant mixture was stirred for 2 hours. The mixture was poured into saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=95/5 to 67/33) to afford a colorless oil. To a CH2Cl2 (25 mL) solution of that colorless oil and tert-butyl 1-piperazinecarboxylate (3.42 g) were added NaBH(OAc)3 (5.310 g) at 0° C. The resultant mixture was stirred at room temperature over night. To the reaction mixture was added saturated aqueous NaHCO3, and extracted with CH2Cl2. The organic layer was washed with saturated aqueous NaCl, dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=67/33 to 33/67) to afford a colorless oil. To a THF (25 mL) solution of that colorless oil was added TBAF (25.05 mL, 1.0 M in THF) at 0° C. The resultant mixture was stirred at room temperature for 1 hour. After cooling to 0° C., the reaction mixture was diluted with AcOEt and water. The organic layer was washed with saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=67/33 to 1/4) to afford tert-butyl 4-[3-fluoro-4-(hydroxymethyl)benzyl]piperazine-1-carboxylate as a colorless oil (2.303 g).

Provenance & Evidence