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

Participants

Reaction Steps

To a solution of 4.09 g of N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2-methyl-propionamide in anh. THF (70 mL) was added dropwise at 0° C. for 15 min a 1M solution of borane-THF complex in THF (87 mL). The mixture was stirred for 25 min at rt then for 1.5 h at 65° C. It was cooled down to 0° C., quenched with 1M-NaOH and extracted with DCM. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude as borane complex was dissolved in MeOH (60 mL) and treated with ethylene diamine (2.37 mL) under microwave conditions (120° C. for 180 s). The mixture was concentrated in vacuo and the resulting residue was taken up in DCM. The organic phase was washed with brine, dried over anh. Na2SO4 and concentrated in vacuo. The oily crude was purified by CC using EtOAc/MeOH/NEt3 from 95/5/1 to 60/40/1 as eluant to yield 2.74 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 as yellowish oil.

Provenance & Evidence