Formaldehyde → (E)-methyl 4-(cyclobutyl(methyl)amino)but-2-enoate

To a solution of (E)-methyl 4-(cyclobutylamino)but-2-enoate (19) (1.7 g, 10 mmol) in THF (30 mL) was added HCHO solution (3 g, 40 mmol, 40% solution in water). The resulting mixture was stirred for 30 min before introducing NaBH(OAc)3 (3.18 g, 15 mmol). Stirring was continued at RT overnight. After quenching with sat. aq. NaHCO3 solution, the reaction mixture was extracted with EA (3×). The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash chromatography (0-5% methanol in DCM) to provide (E)-methyl 4-(cyclobutyl(methyl)amino)but-2-enoate (20) (1.47 g, 80%) as an oil. LC-MS (ESI): m/z (M+1) 184.3.

1. stirringStirring
2. waitwas continued at RT overnight
3. customAfter quenching with sat. aq. NaHCO3 solution
4. extractionthe reaction mixture was extracted with EA (3×)
5. customThe layers were separated
6. dry with materialthe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customThe crude product was purified by flash chromatography (0-5% methanol in DCM)

ORD record

ord-8f4326ef512c42d0a47e91c565f80eee

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08377946B1