(Bromomethyl)cyclobutane → N-Methyl-N-methoxy2-oxo-3-cyclobutyl Propanamide

The finely divided Mg was treated with 22.5 mL (0.20 mol) of bromomethylcyclobutane maintaining the internal temperature at <5° C. The resulting mixture was stirred cold for 1 h, then was treated with 26.40 g (0.15 mol) of N,N′-dimethyl-N,N′-dimethoxy oxamide (from Step A) in portions as a solid. The resulting mixture was stirred at 0° C. for 16 h. The reaction was poured onto a mixture of 100 mL conc. HCl and 500 g of ice under N2 atmosphere. The quenched mixture was extracted with 1.5 L of EtOAc. The extract was washed with 500 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 500 g of silica gel using 3:1 v/v hexanes/EtOAc as the eluant afforded 22.3 g (80%) of the title compound: 1H NMR (500 MHz) δ 1.66-1.76 (m, 2H), 1.82-1.98 (m, 2H), 2.12-2.22 (m, 2H), 2.74-2.84 (3H), 3.20 (s, 3H), 3.66 (s, 3H).

1. stirringThe resulting mixture was stirred at 0° C. for 16 h
2. extractionThe quenched mixture was extracted with 1.5 L of EtOAc
3. washThe extract was washed with 500 mL of sat'd NaCl
4. dry with materialdried over MgSO4
5. concentrationconcentrated

ORD record

ord-3c822f612dd6446792f17d884455e03c

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06498161B1