Methyl iodide → (3R,5S)-1-t-butoxycarbonyl-5-t-butyldiphenylsiloxymethyl-3-methyl-pyrrolidine-2-one

To a solution of (S)-1-t-butoxycarbonyl-5-t-butyldiphenylsiloxymethyl-pyrrolidine-2-one (15 g, 33 mmol) in THF (250 mL) at -78° C. a 1M solution of LiN(SiMe3)2 (35 mL, 35 mmol) was slowly added. After stirring for 1 hr, iodomethane (6.2 mL, 100 mmol) was added. The reaction mixture was allowed to stir for another 2 hr at -78° C. and then quenched with acetic acid. The mixture was concentrated into half volume, diluted with water (200 mL) and extracted with ethyl acetate (EtOAc). The combined extracts were washed with water, brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue purified by flash column chromatography on silica gel, eluted with EtOAc:Hexane (1:2.5). The desired (2S,5R) isomer was eluted first from the column and crystallized in hexanes to give 7.3 g (47%) of product as white crystals. mp=84°-85° C. 1H NMR (200 MHz, CDCl3): δ 7.62 (m, 5H), 7.40 (m, 5H), 4.12 (m, 1H), 3.85 (dd, J=10.3, 4.7 Hz, 1H), 3.72 (dd, J=10.3, 2.8 Hz, 1H), 2.82 (m, 1H), 2.31 (dd, J=12.7, 8.9 Hz, 1H), 1.75 (m, 1H), 1.42 (s, 9H), 1.20 (d, J=7.0 Hz, 3H), 1.02 (s, 9H).

1. stirringto stir for another 2 hr at -78° C.
2. customquenched with acetic acid
3. concentrationThe mixture was concentrated into half volume
4. additiondiluted with water (200 mL)
5. extractionextracted with ethyl acetate (EtOAc)
6. washThe combined extracts were washed with water, brine
7. dry with materialdried over MgSO4
8. customThe solvent was evaporated in vacuo
9. customthe residue purified by flash column chromatography on silica gel
10. washeluted with EtOAc:Hexane (1:2.5)
11. washwas eluted first from the column
12. customcrystallized in hexanes

ORDレコード

ord-10d566a7e6924599b73ffe5a8d4c02d6

出典データセット

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05731348