Bromomethyl methyl ether → 1-tert-Butyl 3-methyl 3-(methoxymethyl)pyrrolidine-1,3-dicarboxylate

Temperature

-78 °C

The title compound was prepared according to general procedure A described in connection with Scheme 2. 1-tert-Butyl 3-methylpyrrolidine-1,3-dicarboxylate (7.27 g, 31.7 mmol) was dissolved in 80 mL of THF under argon. 2M LDA in heptane/THF/Ethylbenzene (19 mL, 38 mmol) was added in 30 min. between −78° C. and −68° C. The reaction mixture was stirred at −78° C. for 45 min. Neat bromo(methoxy)methane (5.25 g, 41.2 mmol) was added over 11 min. at −78° C. The reaction was slowly warmed to RT and stirred for 20 h. The reaction mixture was cooled to −20° C. and quenched with 50 mL 10% NH4Cl. The aqueous layer was extracted with 50 mL EtOAc. The organic layer was washed with 50 mL brine and then dried over Na2SO4. The solvent was evaporated and the resulting residue was purified by 2 flash chromatographies on silica gel using Hexanes/EtOAc 10:1 to 2:1 and 1/3 to give 4.5 g (52% yield) of the desired product. MS (ESI) m/z: Calculated for C13H23NO5: 273.2. found: 295 (M+Na)+.

1. customThe title compound was prepared
2. temperatureThe reaction was slowly warmed to RT
3. stirringstirred for 20 h
4. temperatureThe reaction mixture was cooled to −20° C.
5. customquenched with 50 mL 10% NH4Cl
6. extractionThe aqueous layer was extracted with 50 mL EtOAc
7. washThe organic layer was washed with 50 mL brine
8. dry with materialdried over Na2SO4
9. customThe solvent was evaporated
10. customthe resulting residue was purified by 2 flash chromatographies on silica gel

ORD record

ord-bda56a854da84cc7abcfc629b20f0478

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569282B2