methyl 2-(2-chloropropanoylamino)benzoate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the 2-(2-chloro-propionylamino)-benzoic acid methyl ester (7.75 g, 32.1 mmol) stirring in THF (40 mL) was added 1M LiOH/H2O (40 mL). The reaction was allowed to stir at 50° C. for 3 h. After this period the reaction was concentrated under vacuum to afford a crude residue that was acidified with 1N HCl. The resulting suspension was then diluted with EtOAc and washed with water (3×50 mL). The organic layer was then washed with brine (25 mL), dried over MgSO4, and concentrated under vacuum to afford crude acid. The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex) to afford the desired product as an off white solid (7.1 g, 97% yield). 1H-NMR (CDCl3): δ 8.6 (d, 1H), 8.12 (d, 1H), 7.61 (t, 1H), 7.57 (t, 1H), 4.89 (br, 1H), 4.65 (t, 1H), 1.78 (d, 3H). After this period the reaction was concentrated under vacuum to afford a crude residue that washed with water (3×50 mL) The organic layer was then washed with brine (25 mL) dried over MgSO4 concentrated under vacuum to afford crude acid The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl anthranilate (5 g, 33.1 mmol) stirring in DCM at 0° C. under N2 was added DIEA (5.1 g, 39.7 mmol) in one portion followed by the dropwise addition of 2-chloropropionyl chloride (4.2 g, 33.1 mmol). The reaction was allowed to stir at 0° C. for 30 min. then warmed to room temperature, stirring for an additional 3 h. The reaction was treated with saturated aqueous solution of NaHCO3 and the resulting biphasic mixture transferred to a separatory funnel. The layers separated and the aqueous layer was extracted twice more with DCM (25 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated under vacuum to afford the desired product (7.75 g, 97% yield), which was used without further purification. 1H-NMR (CDCl3): δ 11.8 (br, 1H), 8.72 (dd, 1H), 8.08 (dd, 1H), 7.58 (m, 1H), 7.15 (m, 1H), 4.56 (q, 1H), 3.97 (s, 3H), 1.85 (d, 3H). then warmed to room temperature stirring for an additional 3 h the resulting biphasic mixture transferred to a separatory funnel The layers separated the aqueous layer was extracted twice more with DCM (25 mL) The combined organic layers were washed with brine dried over MgSO4 concentrated under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the 2-(2-chloro-propionylamino)-benzoic acid methyl ester (7.75 g, 32.1 mmol) stirring in THF (40 mL) was added 1M LiOH/H2O (40 mL). The reaction was allowed to stir at 50° C. for 3 h. After this period the reaction was concentrated under vacuum to afford a crude residue that was acidified with 1N HCl. The resulting suspension was then diluted with EtOAc and washed with water (3×50 mL). The organic layer was then washed with brine (25 mL), dried over MgSO4, and concentrated under vacuum to afford crude acid. The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex) to afford the desired product as an off white solid (7.1 g, 97% yield). 1H-NMR (CDCl3): δ 8.6 (d, 1H), 8.12 (d, 1H), 7.61 (t, 1H), 7.57 (t, 1H), 4.89 (br, 1H), 4.65 (t, 1H), 1.78 (d, 3H). After this period the reaction was concentrated under vacuum to afford a crude residue that washed with water (3×50 mL) The organic layer was then washed with brine (25 mL) dried over MgSO4 concentrated under vacuum to afford crude acid The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl anthranilate (5 g, 33.1 mmol) stirring in DCM at 0° C. under N2 was added DIEA (5.1 g, 39.7 mmol) in one portion followed by the dropwise addition of 2-chloropropionyl chloride (4.2 g, 33.1 mmol). The reaction was allowed to stir at 0° C. for 30 min. then warmed to room temperature, stirring for an additional 3 h. The reaction was treated with saturated aqueous solution of NaHCO3 and the resulting biphasic mixture transferred to a separatory funnel. The layers separated and the aqueous layer was extracted twice more with DCM (25 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated under vacuum to afford the desired product (7.75 g, 97% yield), which was used without further purification. 1H-NMR (CDCl3): δ 11.8 (br, 1H), 8.72 (dd, 1H), 8.08 (dd, 1H), 7.58 (m, 1H), 7.15 (m, 1H), 4.56 (q, 1H), 3.97 (s, 3H), 1.85 (d, 3H). then warmed to room temperature stirring for an additional 3 h the resulting biphasic mixture transferred to a separatory funnel The layers separated the aqueous layer was extracted twice more with DCM (25 mL) The combined organic layers were washed with brine dried over MgSO4 concentrated under vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl anthranilate (5 g, 33.1 mmol) stirring in DCM at 0° C. under N2 was added DIEA (5.1 g, 39.7 mmol) in one portion followed by the dropwise addition of 2-chloropropionyl chloride (4.2 g, 33.1 mmol). The reaction was allowed to stir at 0° C. for 30 min. then warmed to room temperature, stirring for an additional 3 h. The reaction was treated with saturated aqueous solution of NaHCO3 and the resulting biphasic mixture transferred to a separatory funnel. The layers separated and the aqueous layer was extracted twice more with DCM (25 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated under vacuum to afford the desired product (7.75 g, 97% yield), which was used without further purification. 1H-NMR (CDCl3): δ 11.8 (br, 1H), 8.72 (dd, 1H), 8.08 (dd, 1H), 7.58 (m, 1H), 7.15 (m, 1H), 4.56 (q, 1H), 3.97 (s, 3H), 1.85 (d, 3H). then warmed to room temperature stirring for an additional 3 h the resulting biphasic mixture transferred to a separatory funnel The layers separated the aqueous layer was extracted twice more with DCM (25 mL) The combined organic layers were washed with brine dried over MgSO4 concentrated under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the 2-(2-chloro-propionylamino)-benzoic acid methyl ester (7.75 g, 32.1 mmol) stirring in THF (40 mL) was added 1M LiOH/H2O (40 mL). The reaction was allowed to stir at 50° C. for 3 h. After this period the reaction was concentrated under vacuum to afford a crude residue that was acidified with 1N HCl. The resulting suspension was then diluted with EtOAc and washed with water (3×50 mL). The organic layer was then washed with brine (25 mL), dried over MgSO4, and concentrated under vacuum to afford crude acid. The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex) to afford the desired product as an off white solid (7.1 g, 97% yield). 1H-NMR (CDCl3): δ 8.6 (d, 1H), 8.12 (d, 1H), 7.61 (t, 1H), 7.57 (t, 1H), 4.89 (br, 1H), 4.65 (t, 1H), 1.78 (d, 3H). After this period the reaction was concentrated under vacuum to afford a crude residue that washed with water (3×50 mL) The organic layer was then washed with brine (25 mL) dried over MgSO4 concentrated under vacuum to afford crude acid The crude material was purified by flash chromatography (silica gel, 80% EtOAc/Hex)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl anthranilate (5 g, 33.1 mmol) stirring in DCM at 0° C. under N2 was added DIEA (5.1 g, 39.7 mmol) in one portion followed by the dropwise addition of 2-chloropropionyl chloride (4.2 g, 33.1 mmol). The reaction was allowed to stir at 0° C. for 30 min. then warmed to room temperature, stirring for an additional 3 h. The reaction was treated with saturated aqueous solution of NaHCO3 and the resulting biphasic mixture transferred to a separatory funnel. The layers separated and the aqueous layer was extracted twice more with DCM (25 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated under vacuum to afford the desired product (7.75 g, 97% yield), which was used without further purification. 1H-NMR (CDCl3): δ 11.8 (br, 1H), 8.72 (dd, 1H), 8.08 (dd, 1H), 7.58 (m, 1H), 7.15 (m, 1H), 4.56 (q, 1H), 3.97 (s, 3H), 1.85 (d, 3H). then warmed to room temperature stirring for an additional 3 h the resulting biphasic mixture transferred to a separatory funnel The layers separated the aqueous layer was extracted twice more with DCM (25 mL) The combined organic layers were washed with brine dried over MgSO4 concentrated under vacuum