Reaction SMILES: Cl.CN[O:4][CH3:5].[Br:6][C:7]1[CH:8]=[C:9]([C:12](Cl)=[O:13])[O:10][CH:11]=1.C([N:18]([CH2:22]C)C(C)C)(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:5][O:4][CH2:22][NH:18][C:12]([C:9]1[O:10][CH:11]=[C:7]([Br:6])[CH:8]=1)=[O:13]
Reactant: CCN(C(C)C)C(C)C
Reactant: O=C(Cl)c1cc(Br)co1
Reactant: CNOC
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: COCNC(=O)c1cc(Br)co1
Temperature: 25 °C
Reaction time: 16 h
Yield: 44 %

Procedure:
A 1 L round bottom flask was charged with N,O-dimethylhydroxylamine hydrochloride (16.9 g, 173 mmol), 4-(N,N-dimethylamino)pyridine (˜100 mg, catalytic) and CH2Cl2 (250 mL). This suspension was then cooled in an ice bath. The 4-bromofuran-2-carbonyl chloride (127 mmol crude) was dissolved in CH2Cl2 (250 mL) containing N,N-diisopropylethylamine (70 mL, 400 mmol). The resulting dark mixture was cooled in an ice bath and then added via cannula to the cold N,O-dimethylhydroxylamine hydrochloride suspension. The acid chloride was not completely soluble, and was treated with further portions of CH2Cl2 (2×50 mL) in an attempt to solubilize the remaining material. These additional washes were added via cannula to the reaction mixture. There were still residual solids remaining in the acid chloride containing flask. A portion of the reaction solution was transferred via cannula to the acid chloride containing flask and was successful in solubilizing the remaining solids in the flask. This solution was transferred back to the reaction flask, and then the acid chloride flask was rinsed with additional CH2Cl2 (50 mL) which was added via cannula to the reaction flask to insure complete transfer. After the completion of the addition, the ice bath was removed and the dark reaction solution was allowed to warm to ambient temperature. After stirring at ambient temperature for 16 hours, TLC analysis showed the desired product to be present by comparison with authentic product. The dark reaction mixture was quenched by the addition of ice-cold H2O (300 mL) and dilution with additional CH2Cl2 (500 mL). A large quantity of off-white solids appeared after the biphasic mixture was transferred to a 2 L separatory funnel. Portions of 1 N HCl were added with occasional shaking in order to dissolve the solids. The layers were separated and the aqueous was extracted with CH2Cl2 (1×100 mL). The combined CH2Cl2 extracts were washed with 1 N HCl (100 mL), H2O (100 mL), then saturated aqueous NaHCO3 (100 mL). The dark organic solution was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a dark brown solid. The solid was taken up in a minimum of CH2Cl2 and loaded onto a Biotage Flash 65 silica gel cartridge pre-conditioned with hexanes. Two-hundred milliliter fractions were collected as the column was eluted with 1 L portions of 10% followed by 15%, 20%, 25%, and finally 30% EtOAc/hexanes. There were closely eluting byproducts that eluted just before, and just after the desired product. Pure product containing fractions from the column were combined and concentrated to afford 4-bromofuran-2-carboxylic acid methoxymethylamide as an off-white solid (13.1 g, 44% yield over three steps). Impure product containing fractions were combined, concentrated, and re-chromatographed as before. Additional pure 4-bromofuran-2-carboxylic acid methoxymethylamide was obtained as an off-white solid (4.75 g, 16% yield over three steps). Some impure product fractions were obtained also. The total isolated yield for the three steps was 60%. 1H-NMR (400 MHz, CDCl3): δ 7.60 (1H, d, J=0.8 Hz), 7.14 (1H, d, J=0.8 Hz), 3.77 (3H, s), 3.35 (3H, s).