Fluoroacetyl chloride → 2-fluoro-N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-N-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2.73 g of (1S,2S)-6-fluoro-1-isopropyl-2-(2-{[3-(3-methoxy-2-methoxymethyl-2-methyl-propylamino)-propyl]-methyl-amino}-ethyl)-1,2,3,4-tetrahydro-naphthalen-2-ol in DCM (29 mL) was added at 0° C., 1.5 mL of DIPEA and 1.1 mL of fluoroacetyl chloride. The mixture was stirred for 20 min at 0° C. then allowed to warm up to rt for 1 h and quenched with sat.-NaHCO3. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude ester was dissolved in EtOH (29 mL) and treated with 15 mL of a 1M NaOH solution. The mixture was stirred for 15 min at rt and concentrated in vacuo. The resulting residue was taken up in DCM and washed with sat.-NaHCO3 and brine. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude was purified by CC using EtOAc/MeOH/NEt3 from 100/0/1 to 90/10/1 to yield 2.07 g of 2-fluoro-N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-N-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-acetamide as orange oil.

Provenance & Evidence