Tributylphosphine → 2-{(2R)-1-[(4-Fluorophenyl)sulfonyl]aziridin-2-yl}ethanol

To a solution of 4-fluoro-N-[(1R)-3-hydroxy-1-(hydroxymethyl)propyl]benzene-sulfonamide (1 equiv) from step 2 in THF (20 mL/g) was added azodicarboxylic acid dipiperidide (1 equiv) followed by tri-n-butylphosphine (1 equiv) dropwise over 30 min. The reaction was stirred for 30 min then filtered. The filtrate was washed with THF and H2O (5 mL/g), then added to the resulting solution and stirred for 1 h. NaCl was added to separate the aqueous and organic layers. The layers were cut and the organic layer washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was triturated in MTBE and filtered. The resulting solution was concentrated and triturated in EtOAc/Hex (1:1) and then filtered. The resulting solution was then concentrated and purified by column chromatography with EtOAc/Hex 25-75% to give the desired material (77%) as a light yellow oil.

1. filtrationthen filtered
2. washThe filtrate was washed with THF and H2O (5 mL/g)
3. additionadded to the resulting solution
4. stirringstirred for 1 h
5. additionNaCl was added
6. customto separate the aqueous and organic layers
7. washthe organic layer washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe crude product was triturated in MTBE
11. filtrationfiltered
12. concentrationThe resulting solution was concentrated
13. customtriturated in EtOAc/Hex (1:1)
14. filtrationfiltered
15. concentrationThe resulting solution was then concentrated
16. custompurified by column chromatography with EtOAc/Hex 25-75%

ORD record

ord-4cd465fc8b2d47db8fda3e28379384fa

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637541B2