Lithium Hexamethyldisilazide → Methyl(1R,4S)-4-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopent-2-ene-1-carboxylate

Temperature

-78 °C

To a 1.00 M solution of lithium hexamethyldisilazide in tetrahydrofuran (34.8 mL, 34.8 mmol) under N2 at −78° C. was added a solution of methyl (1R,4S)-4-[(tert-butoxycarbonyl)amino]cyclopent-2-ene-1-carboxylate (4.0 g, 16 mmol) in tetrahydrofuran (20 mL). The resulting brown solution was stirred at −78° C. for 30 min before adding a solution of (3R)-3-iodotetrahydrofuran (3.75 g, 17.4 mmol) in THF (3 mL). The mixture was stirred for 10 min at −78° C. then kept in a freezer reading at −25° C. overnight. The reaction was quenched with saturated ammonium chloride, extracted with ether three times. The combined extracts were dried (MgSO4), filtered, concentrated and purified by flash column chromatography (EtOAc/Hexane) to provide the desired product (1.6 g, 31%). MS calculated for C16H25NO5: (M+H) 312.2; found 312.2.

1. stirringThe mixture was stirred for 10 min at −78° C.
2. waitthen kept in a freezer reading at −25° C. overnight
3. customThe reaction was quenched with saturated ammonium chloride
4. extractionextracted with ether three times
5. dry with materialThe combined extracts were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified by flash column chromatography (EtOAc/Hexane)

ORD record

ord-d207099a6b0945f496ac4edd9a49072c

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563582B2