3-[[(1,1-Dimethylethoxy)carbonyl]amino]-L-alanine methyl ester

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

Conditions: temp:127.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.8 g (20 mmol) of 1-chloro-2-(2-chloroethoxy)ethane are added to a solution of 5 g (20 mmol) of commercial methyl(S)-2-amino-3-tert-butoxycarbonylaminopropanoate in 65 ml of diisopropylethylamine. The reaction mixture is stirred at 127° C. for 18 h. After the addition of water, the reaction medium is extracted with ethyl acetate. The organic phases are combined, dried over sodium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on silica gel, elution being carried out with a 70/30 heptane/ethyl acetate mixture. 1.4 g (24%) of methyl(S)-3-tert-butoxycarbonylamino-2-morpholin-4-ylpropanoate are obtained in the form of an oil. the reaction medium is extracted with ethyl acetate dried over sodium sulfate filtered evaporated The residue obtained is purified by chromatography on silica gel, elution

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated

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

Procedure: DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. After 12 hours at rt The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml) dried with Na2SO4 filtered concentrated under reduced pressure to give crude product The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1) The fractions with product were evaporated