methyl 6-amino-6-oxohexanoate

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

Procedure: Combine 2-bromo-1-(2-trifluoromethyl-phenyl)-ethanone (6.6 g, 24.7 mmol) with 5-carbamoyl-pentanoic acid methyl ester (7.8 g, 49 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4.5 hours. Cool the mixture, dilute with water, and extract with EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CH2Cl2) allows for recovery of 5-[4-(2-trifluoromethyl-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (3.47 g, 43%). MS (ES): (M+1)+ 328.2 m/z. Cool the mixture extract with EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-Bromo-1-(2-methoxy-phenyl)-propan-1-one (7.25 g, 29.8 mmol) with 5-carbamoyl-pentanoic acid methyl ester (9.5 g, 60.5 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4 h. Cool the mixture, transfer to a flask using methanol and concentrate. Partition the residue between water and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (MeOH/CH2Cl2) allows for recovery of 5-[4-(2-methoxy-phenyl)-5-methyl-oxazol-2-yl]-pentanoic acid methyl ester (3.63 g, 40%). MS (ES): (M+1)+ 304.2 m/z. Cool the mixture, transfer to a flask concentrate Partition the residue between water and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(5-chloro-2-methoxy-phenyl)-ethanone (12.0 g, 46 mmol) with 5-carbamoyl-pentanoic acid methyl ester (12.7 g, 79.9 mmol) and heat the neat mixture in a sealed vessel at 120-140° C. for about 6 h. Cool the mixture and add methanol and allow the mixture to stir overnight at room temperature. Concentrate the mixture and partition the residue between aq NaHCO3 and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CHCl3) allows for recovery of 5-[4-(5-chloro-2-methoxy-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (5.5 g, 37%). MS (ES): (M+1)+ 324.1, 326.1 m/z. Cool the mixture Concentrate the mixture partition the residue between aq NaHCO3 and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(5-chloro-2-methoxy-phenyl)-ethanone (12.0 g, 46 mmol) with 5-carbamoyl-pentanoic acid methyl ester (12.7 g, 79.9 mmol) and heat the neat mixture in a sealed vessel at 120-140° C. for about 6 h. Cool the mixture and add methanol and allow the mixture to stir overnight at room temperature. Concentrate the mixture and partition the residue between aq NaHCO3 and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CHCl3) allows for recovery of 5-[4-(5-chloro-2-methoxy-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (5.5 g, 37%). MS (ES): (M+1)+ 324.1, 326.1 m/z. Cool the mixture Concentrate the mixture partition the residue between aq NaHCO3 and EtOAc Dry the combined extracts over Na2SO4 concentrate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add boron trifluoride etherate (0.30 mL, 1.00 mmol) to a sealed tube containing 2-bromo-1-(3-methoxy-pyridin-2-yl)-ethanone (231 mg, 1.00 mmol), 5-carbamoyl-pentanoic acid methyl ester (222 mg, 1.39 mmol), and THF (anhydrous, 3 mL). Flush with N2, seal, heat at 80° C. overnight. Partition between saturated aqueous NaHCO3 solution and 20% i-PrOH/CHCl3, separate layers. Extract from aqueous layer with 20% i-PrOH/CHCl3 (×3), dry combined organic layers with MgSO4 and concentrate. Adsorb on SiO2 and purify by flash chromatography on silica gel eluting with 1-3% methanol/CHCl3 to afford the title compound (97 mg, 33%). MS (IS) 291 (M+1)+. Flush with N2 seal Partition between saturated aqueous NaHCO3 solution and 20% i-PrOH/CHCl3 separate layers Extract from aqueous layer with 20% i-PrOH/CHCl3 (×3) dry combined organic layers with MgSO4 concentrate purify by flash chromatography on silica gel eluting with 1-3% methanol/CHCl3

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

Procedure: Combine 2-bromo-1-(2-trifluoromethyl-phenyl)-ethanone (6.6 g, 24.7 mmol) with 5-carbamoyl-pentanoic acid methyl ester (7.8 g, 49 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4.5 hours. Cool the mixture, dilute with water, and extract with EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CH2Cl2) allows for recovery of 5-[4-(2-trifluoromethyl-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (3.47 g, 43%). MS (ES): (M+1)+ 328.2 m/z. Cool the mixture extract with EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-Bromo-1-(2-methoxy-phenyl)-propan-1-one (7.25 g, 29.8 mmol) with 5-carbamoyl-pentanoic acid methyl ester (9.5 g, 60.5 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4 h. Cool the mixture, transfer to a flask using methanol and concentrate. Partition the residue between water and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (MeOH/CH2Cl2) allows for recovery of 5-[4-(2-methoxy-phenyl)-5-methyl-oxazol-2-yl]-pentanoic acid methyl ester (3.63 g, 40%). MS (ES): (M+1)+ 304.2 m/z. Cool the mixture, transfer to a flask concentrate Partition the residue between water and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(5-chloro-2-methoxy-phenyl)-ethanone (12.0 g, 46 mmol) with 5-carbamoyl-pentanoic acid methyl ester (12.7 g, 79.9 mmol) and heat the neat mixture in a sealed vessel at 120-140° C. for about 6 h. Cool the mixture and add methanol and allow the mixture to stir overnight at room temperature. Concentrate the mixture and partition the residue between aq NaHCO3 and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CHCl3) allows for recovery of 5-[4-(5-chloro-2-methoxy-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (5.5 g, 37%). MS (ES): (M+1)+ 324.1, 326.1 m/z. Cool the mixture Concentrate the mixture partition the residue between aq NaHCO3 and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(2-trifluoromethyl-phenyl)-ethanone (6.6 g, 24.7 mmol) with 5-carbamoyl-pentanoic acid methyl ester (7.8 g, 49 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4.5 hours. Cool the mixture, dilute with water, and extract with EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CH2Cl2) allows for recovery of 5-[4-(2-trifluoromethyl-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (3.47 g, 43%). MS (ES): (M+1)+ 328.2 Cool the mixture extract with EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-Bromo-1-(2-methoxy-phenyl)-propan-1-one (7.25 g, 29.8 mmol) with 5-carbamoyl-pentanoic acid methyl ester (9.5 g, 60.5 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4 h. Cool the mixture, transfer to a flask using methanol and concentrate. Partition the residue between water and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (MeOH/CH2Cl2) allows for recovery of 5-[4-(2-methoxy-phenyl)-5-methyl-oxazol-2-yl]-pentanoic acid methyl ester (3.63 g, 40%). MS (ES): (M+1)+ 304.2 m/z. Cool the mixture, transfer to a flask concentrate Partition the residue between water and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(5-chloro-2-methoxy-phenyl)-ethanone (12.0 g, 46 mmol) with 5-carbamoyl-pentanoic acid methyl ester (12.7 g, 79.9 mmol) and heat the neat mixture in a sealed vessel at 120-140° C. for about 6 h. Cool the mixture and add methanol and allow the mixture to stir overnight at room temperature. Concentrate the mixture and partition the residue between aq NaHCO3 and EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CHCl3) allows for recovery of 5-[4-(5-chloro-2-methoxy-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (5.5 g, 37%). MS (ES): (M+1)+ 324.1, 326.1 m/z. Cool the mixture Concentrate the mixture partition the residue between aq NaHCO3 and EtOAc Dry the combined extracts over Na2SO4 concentrate

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

Procedure: Combine 2-bromo-1-(2-trifluoromethyl-phenyl)-ethanone (6.6 g, 24.7 mmol) with 5-carbamoyl-pentanoic acid methyl ester (7.8 g, 49 mmol) and heat the neat mixture in a sealed vessel at 140-150° C. for about 4.5 hours. Cool the mixture, dilute with water, and extract with EtOAc. Dry the combined extracts over Na2SO4 and concentrate. Chromatography over silica gel (CH2Cl2) allows for recovery of 5-[4-(2-trifluoromethyl-phenyl)-oxazol-2-yl]-pentanoic acid methyl ester (3.47 g, 43%). MS (ES): (M+1)+ 328.2 m/z. Cool the mixture extract with EtOAc Dry the combined extracts over Na2SO4 concentrate