O-TERT-BUTYL-N-CARBOBENZOXY-L-SERINE METHYL ESTER

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8.6 g (96%). The structure was confirmed by 1HNMR and 13CNMR. The mixture was stirred for an additional 20 minutes to reach -50° C the resulting reaction mixture to reach -10° C The organic layer was separated the aqueous layer was extracted with ethylacetate (2×100 ml) The combined organic solution was dried with sodium sulphate evaporated to dryness below 40° C. (bath temperature)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8.6 g (96%). The structure was confirmed by 1HNMR and 13CNMR. The mixture was stirred for an additional 20 minutes to reach -50° C the resulting reaction mixture to reach -10° C The organic layer was separated the aqueous layer was extracted with ethylacetate (2×100 ml) The combined organic solution was dried with sodium sulphate evaporated to dryness below 40° C. (bath temperature)

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

Procedure: N-Boc-O-benzylserine-hydroxysuccinimide (16.0 g, 40.8 mmol) was dissolved in methanol (300 ml) and stirred at 50° C. for 24 hours. The solvent was evaporated and the residue was taken up in ethyl acetate (120 ml), washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml). The organic solution was dried with sodium sulphate and after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil. Yield 9.9 g (83%). The structure was confirmed by 1HNMR and 13CNMR. The solvent was evaporated washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml) The organic solution was dried with sodium sulphate after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8.6 g (96%). The structure was confirmed by 1HNMR and 13CNMR. The mixture was stirred for an additional 20 minutes to reach -50° C the resulting reaction mixture to reach -10° C The organic layer was separated the aqueous layer was extracted with ethylacetate (2×100 ml) The combined organic solution was dried with sodium sulphate evaporated to dryness below 40° C. (bath temperature)

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

Procedure: N-Boc-O-benzylserine-hydroxysuccinimide (16.0 g, 40.8 mmol) was dissolved in methanol (300 ml) and stirred at 50° C. for 24 hours. The solvent was evaporated and the residue was taken up in ethyl acetate (120 ml), washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml). The organic solution was dried with sodium sulphate and after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil. Yield 9.9 g (83%). The structure was confirmed by 1HNMR and 13CNMR. The solvent was evaporated washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml) The organic solution was dried with sodium sulphate after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil

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

Procedure: A mixture of BOC-DL-Ser-OMe (434 mg, 2.0 mmol), benzyl bromide (513 mg, 3.0 mmol), and silver oxide (695 mg, 3.0 mmol) in dichloromethane (10 mL) at room temperature was stirred for 2 days, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes to provide the desired product. MS (ESI(−)) m/e 308 (M−H)−. filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes

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

Procedure: A mixture of BOC-DL-Ser-OMe (434 mg, 2.0 mmol), benzyl bromide (513 mg, 3.0 mmol), and silver oxide (695 mg, 3.0 mmol) in dichloromethane (10 mL) at room temperature was stirred for 2 days, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes to provide the desired product. MS (ESI(−)) m/e 308 (M−H)−. filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes

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

Procedure: A mixture of BOC-DL-Ser-OMe (434 mg, 2.0 mmol), benzyl bromide (513 mg, 3.0 mmol), and silver oxide (695 mg, 3.0 mmol) in dichloromethane (10 mL) at room temperature was stirred for 2 days, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes to provide the desired product. MS (ESI(−)) m/e 308 (M−H)−. filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 20% ethyl acetate/hexanes

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8.6 g (96%). The structure was confirmed by 1HNMR and 13CNMR. The mixture was stirred for an additional 20 minutes to reach -50° C the resulting reaction mixture to reach -10° C The organic layer was separated the aqueous layer was extracted with ethylacetate (2×100 ml) The combined organic solution was dried with sodium sulphate evaporated to dryness below 40° C. (bath temperature)

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

Procedure: N-Boc-O-benzylserine-hydroxysuccinimide (16.0 g, 40.8 mmol) was dissolved in methanol (300 ml) and stirred at 50° C. for 24 hours. The solvent was evaporated and the residue was taken up in ethyl acetate (120 ml), washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml). The organic solution was dried with sodium sulphate and after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil. Yield 9.9 g (83%). The structure was confirmed by 1HNMR and 13CNMR. The solvent was evaporated washed with aqueous saturated sodium bicarbonate (2×50 ml) and water (50 ml) The organic solution was dried with sodium sulphate after evaporation of the solvent the N-Boc-O-benzylserine methyl ester was isolated as a colourless oil

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8 6 g (96%). The structure was confirmed by 1HNMR and 13CNMR. The mixture was stirred for an additional 20 minutes to reach -50° C the resulting reaction mixture to reach -10° C The organic layer was separated the aqueous layer was extracted with ethylacetate (2×100 ml) The combined organic solution was dried with sodium sulphate evaporated to dryness below 40° C. (bath temperature)

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

Procedure: (O-benzyl) Boc Serine 2.00 g (6.8 mmoles) was dissolved in 50 ml of ether. To this solution was added an ether solution containing freshly prepared diazomethane prepared from 5 g of Diazald using the procedure from Aldrich Technical Bulletin number AL-180. After stirring the solution for 30 minutes, glacial acetic acid was added dropwise until the solution became clear. The resulting solution was concentrated in vacuo to yield 2.00 g, 95% as a clear oil. 1H: (CDCl3); 7.3 (d, 5H), 5.5 (bs, 1H), 4.5 (s, 2H), 3.8 (m, 2H), 3.7 (s, 3H), 1.4 (s, 9H) The resulting solution was concentrated in vacuo to yield 2.00 g, 95% as a clear oil