2,4-dibromo-N-methylbutanamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a second step of the reaction, the methyl-2,4-dibromobutyrate is reacted with methylamine in an aqueous solution at a temperature of below ambient in order to form N-methyl-2,4-dibromobutyramide. Then butyramide is then recovered and purified to obtain the solid intermediate product. In a second step of the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: There is also provided by this invention a method for preparation of 3-hydroxy-N-methylpyrrolidone which comprises conversion of delta-butyrolactone to methyl-2,4-dibromobutyrate, conversion of the methyl-2,4-dibromobutyrate to N-methyl-2,4-dibromobutyramide, ring closure of the N-methyl-2,4-dibromobutyramide to form 3-bromo-N-methyl-2-pyrrolidone, and conversion of the 3-bromo-N-methyl-2-pyrrolidone to 3-hydroxy-N-methyl-2-pyrrolidone by reaction with alkali metal carbonate. There is also provided by this invention a method

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: There is also provided by this invention a method for preparation of 3-hydroxy-N-methylpyrrolidone which comprises conversion of delta-butyrolactone to methyl-2,4-dibromobutyrate, conversion of the methyl-2,4-dibromobutyrate to N-methyl-2,4-dibromobutyramide, ring closure of the N-methyl-2,4-dibromobutyramide to form 3-bromo-N-methyl-2-pyrrolidone, and conversion of the 3-bromo-N-methyl-2-pyrrolidone to 3-hydroxy-N-methyl-2-pyrrolidone by reaction with alkali metal carbonate. There is also provided by this invention a method

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: reacting the methyl-2,4-dibromobutyrate with methylamine in an aqueous medium to form N-methyl-2,4-dibromobutyramide;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4-dibromobutyrate (50 gm, 0.192 mole) was mixed with 40 wt % methylamine in aqueous solution (20.0 ml, 7.22 gm, 0.232 mole) with stirring and cooling in an ice bath. The reaction mixture was stirred for 16 hours at 5° C., chloroform (100 ml) was then added and the organic layer washed with water. The organic extract was dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by column chromatography (silica gel, gradient elution hexane/chloroform to chloroform/ethylacetate) to yield an off-white solid, (25.4 gm, 51.7%): m.p. 42°-47° C. The compound was used in the next step without further purification. A small portion was further purified for elemental analysis; m.p. 48°-49° C. IR(KBr) 3450, 1660, 1570, 1415, 1240 and 1210 cm-1 ; H-NMR (CDCl3) δ 2.48 (m, 1H, --CH2 -CHBr--), 2.79(m, 1H, --CH2 -CHBy--), (d, 3H, --NH2 -CH3 --), 3.55 (t, 2H, Br--CH2 --CH2), 4.54 (dd, 1H, --CHBr--); 6.39 (s, broad, 1H, --NH--CH3), C--NMR, decoupled (CDCl3) 26.83, 30.27, 37.60, 48.26, 168.65 ppm. Anal. calcd. for C5H9NBr2O (258.949): C, 23.19; H, 3.50; N, 5.41. Found: C, 23.53; H, 3.44; N, 5.29%. cooling in an ice bath The reaction mixture was stirred for 16 hours at 5° C. the organic layer washed with water The organic extract was dried over magnesium sulfate filtered the solvent removed The crude product was purified by column chromatography (silica gel, gradient elution hexane/chloroform to chloroform/ethylacetate) to yield an off-white solid, (25.4 gm, 51.7%) The compound was used in the next step without further purification A small portion was further purified for elemental analysis

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4-dibromobutyrate (50 gm, 0.192 mole) was mixed with 40 wt % methylamine in aqueous solution (20.0 ml, 7.22 gm, 0.232 mole) with stirring and cooling in an ice bath. The reaction mixture was stirred for 16 hours at 5° C., chloroform (100 ml) was then added and the organic layer washed with water. The organic extract was dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by column chromatography (silica gel, gradient elution hexane/chloroform to chloroform/ethylacetate) to yield an off-white solid, (25.4 gm, 51.7%): m.p. 42°-47° C. The compound was used in the next step without further purification. A small portion was further purified for elemental analysis; m.p. 48°-49° C. IR(KBr) 3450, 1660, 1570, 1415, 1240 and 1210 cm-1 ; H-NMR (CDCl3) δ 2.48 (m, 1H, --CH2 -CHBr--), 2.79(m, 1H, --CH2 -CHBy--), (d, 3H, --NH2 -CH3 --), 3.55 (t, 2H, Br--CH2 --CH2), 4.54 (dd, 1H, --CHBr--); 6.39 (s, broad, 1H, --NH--CH3), C--NMR, decoupled (CDCl3) 26.83, 30.27, 37.60, 48.26, 168.65 ppm. Anal. calcd. for C5H9NBr2O (258.949): C, 23.19; H, 3.50; N, 5.41. Found: C, 23.53; H, 3.44; N, 5.29%. cooling in an ice bath The reaction mixture was stirred for 16 hours at 5° C. the organic layer washed with water The organic extract was dried over magnesium sulfate filtered the solvent removed The crude product was purified by column chromatography (silica gel, gradient elution hexane/chloroform to chloroform/ethylacetate) to yield an off-white solid, (25.4 gm, 51.7%) The compound was used in the next step without further purification A small portion was further purified for elemental analysis

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a second step of the reaction, the methyl-2,4-dibromobutyrate is reacted with methylamine in an aqueous solution at a temperature of below ambient in order to form N-methyl-2,4-dibromobutyramide. Then butyramide is then recovered and purified to obtain the solid intermediate product. In a second step of the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: There is also provided by this invention a method for preparation of 3-hydroxy-N-methylpyrrolidone which comprises conversion of delta-butyrolactone to methyl-2,4-dibromobutyrate, conversion of the methyl-2,4-dibromobutyrate to N-methyl-2,4-dibromobutyramide, ring closure of the N-methyl-2,4-dibromobutyramide to form 3-bromo-N-methyl-2-pyrrolidone, and conversion of the 3-bromo-N-methyl-2-pyrrolidone to 3-hydroxy-N-methyl-2-pyrrolidone by reaction with alkali metal carbonate. There is also provided by this invention a method

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: There is also provided by this invention a method for preparation of 3-hydroxy-N-methylpyrrolidone which comprises conversion of delta-butyrolactone to methyl-2,4-dibromobutyrate, conversion of the methyl-2,4-dibromobutyrate to N-methyl-2,4-dibromobutyramide, ring closure of the N-methyl-2,4-dibromobutyramide to form 3-bromo-N-methyl-2-pyrrolidone, and conversion of the 3-bromo-N-methyl-2-pyrrolidone to 3-hydroxy-N-methyl-2-pyrrolidone by reaction with alkali metal carbonate. There is also provided by this invention a method

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4-Dibromobutanoyl chloride (CAS no. 82820-87-9) (16.9 g, 64 mmol) in DCM (20 mL) was added dropwise to a solution of methylamine (20 mL) in water (30 mL) and DCM (30 mL) at 10-15° C., then warmed to 30° C. and stirred for 30 minutes. The organic layer was separated and the aqueous layer re-extracted with DCM (2×10 mL), the combined organic layers were washed with brine (20 mL), dried (MgSO4) and evaporated to afford the product (16.3 g, 98%). 1H NMR δ (400 MHz, CDCl3) 2.35-2.45 (m, 1H), 2.57-2.67 (m, 1H), 2.81 (d, 3H), 3.44-3.54 (m, 2H), 4.46 (q, 1H), 6.34 (s, 1H). The organic layer was separated the aqueous layer re-extracted with DCM (2×10 mL) the combined organic layers were washed with brine (20 mL) dried (MgSO4) evaporated

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4-Dibromobutanoyl chloride (CAS no. 82820-87-9) (16.9 g, 64 mmol) in DCM (20 mL) was added dropwise to a solution of methylamine (20 mL) in water (30 mL) and DCM (30 mL) at 10-15° C., then warmed to 30° C. and stirred for 30 minutes. The organic layer was separated and the aqueous layer re-extracted with DCM (2×10 mL), the combined organic layers were washed with brine (20 mL), dried (MgSO4) and evaporated to afford the product (16.3 g, 98%). 1H NMR δ (400 MHz, CDCl3) 2.35-2.45 (m, 1H), 2.57-2.67 (m, 1H), 2.81 (d, 3H), 3.44-3.54 (m, 2H), 4.46 (q, 1H), 6.34 (s, 1H). The organic layer was separated the aqueous layer re-extracted with DCM (2×10 mL) the combined organic layers were washed with brine (20 mL) dried (MgSO4) evaporated