Triethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamide

Temperature

0 °C

To a CH2Cl2 (5 ml) solution of tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propylcarbamate (Diastereomer B). (0.47 g, 0.79 mmol), at r.t., was added 25 ml of 20% TFA/CH2Cl2. The mixture was stirred at r.t for 30 min. The solvent was removed in vacuo and the residue dissolved in CH2Cl2 (75 ml) and washed with aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield a white foam. The residue was dissolved in CH2Cl2 (5 ml) and chilled to 0° C. followed by the addition of Et3N (0.24 ml, 1.7 mmol) and acetyl imidazole (0.10 g, 0.90 mmol). The mixture was then warmed to r.t. and stirred overnight. The reaction mixture was diluted with CH2Cl2 (25 ml) and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield a white foam (0.35 g, 84%) after flash chromatograph 5% MeOH/CHCl3 (Biotage 40 S). Rf=0.29. HRMS (ESI+) calcd for C22H25N2O3IF2+1H calcd m/z 531.0958; found 531.0958 (M+H)+.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue dissolved in CH2Cl2 (75 ml)
3. washwashed with aqueous NaHCO3 and brine
4. dry with materialThe organic layer was dried over Na2SO4
5. concentrationconcentrated in vacuo
6. customto yield a white foam
7. temperatureThe mixture was then warmed to r.t.
8. stirringstirred overnight
9. washwashed with water and brine
10. dry with materialThe organic layer was dried over Na2SO4
11. concentrationconcentrated in vacuo

ORD record

ord-3361f59d32d846cb93e48d8f5d3b2458

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07244725B2