methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of methyl (tert-butyloxycarbonyl)glycinate (8.54 g, 45.1 mmol) was added hydrazine hydrate (4.4 mL, 90.5 mmol) and the reaction was heated under reflux for 16 hours. The solvent was removed in vacuo and the residue partitioned between dichloromethane (100 mL) and water (100 mL). The phases were separated, the aqueous phase evaporated in vacuo to low volume and extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to give the product as a white crystalline solid, 5.27 g (62%). the reaction was heated under reflux for 16 hours The solvent was removed in vacuo the residue partitioned between dichloromethane (100 mL) and water (100 mL) The phases were separated the aqueous phase evaporated in vacuo to low volume extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts dried over magnesium sulfate concentrated in vacuo

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

Procedure: To a stirred solution of methyl (tert-butyloxycarbonyl)glycinate (8.54 g, 45.1 mmol) was added hydrazine hydrate (4.4 mL, 90.5 mmol) and the reaction was heated under reflux for 16 hours. The solvent was removed in vacuo and the residue partitioned between dichloromethane (100 mL) and water (100 mL). The phases were separated, the aqueous phase evaporated in vacuo to low volume and extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to give the product as a white crystalline solid, 5.27 g (62%). the reaction was heated under reflux for 16 hours The solvent was removed in vacuo the residue partitioned between dichloromethane (100 mL) and water (100 mL) The phases were separated the aqueous phase evaporated in vacuo to low volume extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts dried over magnesium sulfate concentrated in vacuo

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

Procedure: To a flask containing methyl 2-((tert-butoxycarbonyl)amino)acetate (4.18 g, 22.09 mmol) in anhydrous DMF (50 ml) was added KOtBu (3.99 g, 35.6 mmol) then after 1 min at room temperature added methyl 3-bromo-2-(bromomethyl)benzoate (4.97 g, 16.14 mmol) as a solid in 1 portion. The reaction mixture was then capped (not under N2) & stirred at room temperature for 3 hours. Followed by LC/MS. The reaction mixture was quenched/diluted with sat'd NaHCO3, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-20% EtOAc/Hex; 220 g ISCO); desired fractions concentrated to yield 2-tert-butyl 3-methyl 8-bromo-4-oxo-3,4-dihydroisoquinoline-2,3 (1H)-dicarboxylate (24-1). The reaction mixture was then capped (not under N2) & washed with saturated NaHCO3 organics dried over Na2SO4 filtered concentrated Purification by silica gel chromatography (0-20% EtOAc/Hex; 220 g ISCO) desired fractions concentrated

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

Procedure: Ethylamine (37 g, 0.82 mol) was condensed into a pressure vessel at 0° C. N-(tert-butoxycarbonyl)glycine methyl ester (50 mL, 0.34 mol) was added. The vessel was sealed and the mixture was stirred at room temperature overnight. The product mixture was concentrated under vacuum and the residue was passed through a pad of silica gel eluting with ethyl acetate. The solution was concentrated under vacuum to provide the title compound as a clear oil. condensed into a pressure vessel at 0° C The vessel was sealed The product mixture was concentrated under vacuum The solution was concentrated under vacuum

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of BOC glycine methyl ester (J. Med. Chem. 2001, 44, 8, 1192-1201) (19.2 g, 101.5 mmol) in THF at 0° C. was added dropwise ethyl acrylate (11 mL, 101.5 mmol) over 10 minutes. The solution was stirred for 20 minutes, then KOtBu (111.65 mL, 111.65 mmol) was added over 45 minutes. The solution was allowed to warm to 25° C. overnight. The resulting solution concentrated in vacuo and portioned between ethyl acetate and water containing 5 mL of acetic acid. The ethyl acetate layer was removed and aqueous layer extracted with 2×200 mL of ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford an oil. MS (DCI/NH4) m/z=258 (M+H)+, 275 (M+NH4)+. The resulting solution concentrated in vacuo The ethyl acetate layer was removed aqueous layer extracted with 2×200 mL of ethyl acetate The combined ethyl acetate layers were washed with brine dried over MgSO4 filtered concentrated in vacuo to afford an oil

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

Procedure: To a stirred solution of methyl (tert-butyloxycarbonyl)glycinate (8.54 g, 45.1 mmol) was added hydrazine hydrate (4.4 mL, 90.5 mmol) and the reaction was heated under reflux for 16 hours. The solvent was removed in vacuo and the residue partitioned between dichloromethane (100 mL) and water (100 mL). The phases were separated, the aqueous phase evaporated in vacuo to low volume and extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to give the product as a white crystalline solid, 5.27 g (62%). the reaction was heated under reflux for 16 hours The solvent was removed in vacuo the residue partitioned between dichloromethane (100 mL) and water (100 mL) The phases were separated the aqueous phase evaporated in vacuo to low volume extracted with 5% methanol/dichloromethane (2×100 mL) The organic extracts dried over magnesium sulfate concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: