2-[(2-methylpropan-2-yl)oxycarbonylamino]propanedioic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine t-butoxycarbonylaminomalonic acid (0.438 g, 2.00 mmol), benzylamine (0.436 mL, 4.0 mmol), and dichloromethane (10 mL). Add N-methylmorpholine (0.55 mL, 5.00 mmol) ), 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloric acid salt (0.96 g, 5.0 mmol), and 1-hydroxybenztriazole hydrate (0.67 g, 5.0 mmol). After 18 hours, concentrate in vacuo, dilute the concentrated reaction mixture with ethyl acetate, extract with an aqueous 5% sulfuric acid solution, a saturated sodium bicarbonate solution, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 3/2 ethyl acetate/hexane to give the title compound (52%). concentrate in vacuo dilute the concentrated reaction mixture with ethyl acetate extract with an aqueous 5% sulfuric acid solution Dry the organic layer over Na2SO4 filter evaporate in vacuo to give a residue

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine a mixture of t-butoxycarbonylaminomalonic acid and sodium chloride from Preparation 1.2 (5.0 g, 13.7 mmol), phenethylamine (4.32 mL, 34.3 mmol), and tetrahydrofuran (25 mL). Cool in an ice bath. Remove the ice bath. Add N-methylmorpholine (3.8 mL, 34.3 mmol), 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloric acid salt (6.58 g, 34.3 mmol), and 1-hydroxybenztriazole hydrate (4.63 g, 34.3 mmol). Allow to warm to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate, extract with an aqueous 5% sulfuric acid solution, a saturated sodium bicarbonate solution, and then brine. Dry the organic layers over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 2/1 ethyl acetate/hexane to give the title compound (84%). Cool in an ice bath Remove the ice bath extract with an aqueous 5% sulfuric acid solution Dry the organic layers over Na2SO4 filter evaporate in vacuo to give a residue

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine t-butoxycarbonylaminomalonic acid (0.465 g, 2.12 mmol), phenethylamine (0.715 mL, 5.70 mmol), and dichloromethane (25 mL). Add N-methylmorpholine (0.752 mL, 6.85 mmol). Cool in an ice bath. Add benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate complex (3.15 g, 6.85 mmol). Remove the ice bath and allow to warm to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate, extract with an aqueous 5% sulfuric acid solution, a saturated sodium bicarbonate solution, and then brine. Dry the organic layers over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 2/1 ethyl acetate/hexane to give the title compound. Cool in an ice bath Remove the ice bath dilute the reaction mixture with ethyl acetate extract with an aqueous 5% sulfuric acid solution Dry the organic layers over Na2SO4 filter evaporate in vacuo to give a residue

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine diethyl t-butoxycarbonylaminomalonate (4.55 g, 16.5 mmol), a 6 M aqueous sodium hydroxide solution (6.65 mL, 40 mmol), and ethanol (30 mL). After 18 hours, evaporate in vacuo to remove most of the ethanol, dilute with water (50 mL) and extract with diethyl ether. Acidify to a pH of about 3 with aqueous 12M hydrochloric acid and extract twice with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to give the title compound (61%). evaporate in vacuo to remove most of the ethanol dilute with water (50 mL) extract with diethyl ether extract twice with ethyl acetate Dry the combined organic layers over Na2SO4 filter concentrate in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine diethyl t-butoxycarbonylaminomalonate (4.55 g, 16.5 mmol), a 6 M aqueous sodium hydroxide solution (6.65 mL, 40 mmol), and ethanol (30 mL). After 18 hours, evaporate in vacuo to remove most of the ethanol, dilute with water (50 mL) and extract with diethyl ether. Acidify to a pH of about 3 with aqueous 12M hydrochloric acid and extract twice with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to give the title compound (61%). evaporate in vacuo to remove most of the ethanol dilute with water (50 mL) extract with diethyl ether extract twice with ethyl acetate Dry the combined organic layers over Na2SO4 filter concentrate in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine diethyl t-butoxycarbonylaminomalonate (4.55 g, 16.5 mmol), a 6 M aqueous sodium hydroxide solution (6.65 mL, 40 mmol), and ethanol (30 mL). After 18 hours, evaporate in vacuo to remove most of the ethanol, dilute with water (50 mL) and extract with diethyl ether. Acidify to a pH of about 3 with aqueous 12M hydrochloric acid and extract twice with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to give the title compound (61%). evaporate in vacuo to remove most of the ethanol dilute with water (50 mL) extract with diethyl ether extract twice with ethyl acetate Dry the combined organic layers over Na2SO4 filter concentrate in vacuo