反应详情

To a solution of 2.24 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 in anh. THF (35 mL) was added dropwise at 0° C. for 20 min a 1M solution of borane-THF complex in THF (44 mL). The mixture was stirred for 10 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 (42 mL) and treated with ethylene diamine (1.18 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 100/0/1 to 92/8/1 as eluant to yield 1.51 g of (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-ol as yellowish oil.

1. waitfor 1.5 h at 65° C
2. temperatureIt was cooled down to 0° C.
3. customquenched with 1M-NaOH
4. extractionextracted with DCM
5. dry with materialThe organic phase was dried over anh. Na2SO4
6. concentrationconcentrated in vacuo
7. dissolutionThe resulting crude as borane complex was dissolved in MeOH (42 mL)
8. additiontreated with ethylene diamine (1.18 mL) under microwave conditions (120° C. for 180 s)
9. concentrationThe mixture was concentrated in vacuo
10. washThe organic phase was washed with brine
11. dry with materialdried over anh. Na2SO4
12. concentrationconcentrated in vacuo
13. customThe oily crude was purified by CC