benzyl (2S)-2-amino-3-hydroxypropanoate;hydrochloride

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde (1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). 1H-NMR (300 MHz, CDCl3): δ 3.48 (dd, 1H), 3.64 (dd, 1H), 3.74 (d, 1H), 3.80 (dd, 1H), 3.88 (d, 1H), 5.18 (s, 2H), 7.25-7.39 (m, 10H). MS (M+H+): 286. partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde (1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). 1H-NMR (300 MHz, CDCl3): δ 3.48 (dd, 1H), 3.64 (dd, 1H), 3.74 (d, 1H), 3.80 (dd, 1H), 3.88 (d, 1H), 5.18 (s, 2H), 7.25-7.39 (m, 10H). MS (M+H+): 286. partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde(1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde(1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness

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

Procedure: This compound was prepared from N-Boc-D-homophenylalanine (500 mg) and L-serine benzyl ester hydrochloride (415 mg), with purification by chromatography over silica gel (40% ethyl acetate/hexane) to afford title compound (290 mg) as a glassy solid: 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 9H), 1.97 (m, 1H), 2.18 (m, 1H), 2.70 (m, 2H), 3.98 (m, 2H), 4.19 (m, 1H), 4.64 (m, 1H), 5.29 (bs, 2H), 7.16-7.29 (m, 5H), and 7.36 (bs, 5H).

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

Procedure: To a stirred solution of 2-(benzyloxy)benzoic acid (2.0 g, 8.7 mmol), L-serine benzyl ester hydrochloride (2.0 g, 8.7 mmol, 1 equiv.) and HOAt (1.2 g, 8.7 mmol, 1 equiv.) in DMF (200 mL) was added triethylamine (0.98 mL, 9.6 mmol, 1.1 equiv.) and EDC HCl (2.02 g, 4.8 mmol, 1.2 equiv.). After being stirred overnight at room temperature under nitrogen, the reaction mixture was diluted with ethyl acetate (200 mL), washed with 1N HCl (60 mL), saturated NaHCO3, saturated NH4Cl (60 mL), and brine (60 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel eluting with CH2Cl2/MeOH (95/5) to give the title compound, N-[2-(benzyloxy)benzoyl]-L-serine benzyl ester, 92.5 g, 70%) as white crystals. Rf=0.5 (CH2Cl2/MeOH, 95/5); 1H NMR (300 MHz, CDCl3) δ8.80 (d, 1H, NH), 8.19 (dd,1H, ArH), 7.46-7.24 (m, 11H, ArH), 7.12-7.04 (m, 2H, ArH), 5.21-5.11 (m, 4H, 2{CH2phenyl}), 4.91-4.87 (m, 1H, CH), 3.93-3.90 (m, 2H, CH2OH), 2.2 (1H, OH). washed with 1N HCl (60 mL), saturated NaHCO3, saturated NH4Cl (60 mL), and brine (60 mL) The combined organic layers were dried over Na2SO4 filtered concentrated chromatographed on silica gel eluting with CH2Cl2/MeOH (95/5)

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

Procedure: To a solution of methyl (±)-3-carboxy-4-[4-(triisopropylsilyloxy)phenyl]butanoate (5.00 g, 12.67 mmole) in dry DMF (60 mL) at RT was added serine benzyl ester hydrochloride (3.52 g, 15.21 mmole), HOBt (2.06 g, 15.21 mmole), Et3N (5.3 mL, 38.01 mmole), and EDC (2.92 g, 15.21 mmole). After 18 hr the mixture was concentrated. The residue was chromatographed on silica gel (80% EtOAc/hexanes) to give the title compound (5.76 mg, 79%) as a pale yellow oil: MS (ES) m/e 572 (M+H)+. After 18 hr the mixture was concentrated The residue was chromatographed on silica gel (80% EtOAc/hexanes)

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

Procedure: This compound was prepared from N-Boc-D-homophenylalanine (500 mg) and L-serine benzyl ester hydrochloride (415 mg), with purification by chromatography over silica gel (40% ethyl acetate/hexane) to afford title compound (290 mg) as a glassy solid: 1H NMR (400 Mz, CDCl3) δ1.42 (s, 9H), 1.97 (m, 1H), 2.18 (m, 1H), 2.70 (m, 2H), 3.98 (m, 2H), 4.19 (m, 1H), 4.64 (m, 1H), 5.29 (bs, 2H), 7.16-7.29 (m, 5H), and 7.36 (bs, 5H).

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde (1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). 1H-NMR (300 MHz, CDCl3): δ 3.48 (dd, 1H), 3.64 (dd, 1H), 3.74 (d, 1H), 3.80 (dd, 1H), 3.88 (d, 1H), 5.18 (s, 2H), 7.25-7.39 (m, 10H). MS (M+H+): 286. partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness

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

Procedure: To a mixture of L-serine-benzyl ester-HCl (2.3 g), benzaldehyde(1.05 eq.) and sodium acetate (1 eq.) in methanol was added sodium cyanoborohydride (1.0 eq.). The resulting mixture was stirred at ambient temperature for 15 hrs, then partitioned into ether and aqueous saturated sodium bicarbonate. The separated organic phase was extracted with 1M HCl (3×). Combined aqueous extracts were washed with ether, basified with aqueous 4.5M K2CO3 and extracted with ether. Combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 2.32 g of the desired compound (waxy solid, 81% yield). partitioned into ether and aqueous saturated sodium bicarbonate The separated organic phase was extracted with 1M HCl (3×) Combined aqueous extracts were washed with ether extracted with ether Combined organic extracts were washed with brine dried over sodium sulfate concentrated to dryness