ethyl (2R)-2-hydroxypropanoate

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.7 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-bromophenol (8.65 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (12.2 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.74 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-phenylphenol (8.51 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (11.3 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared from 3-amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide, trifluoroacetate (Example 107, Step C) and (R)-2-benzyloxypropanol (prepared from ethyl-D-lactate according to the procedure of Hanessian and Kloss, Tetrahedron Lett. 1985, 26, 1261-1264.) by the procedure described in Example 86, Step A. 1H NMR (200 MHz,CD3OD): 1.31 (d,6 Hz,3H), 1.4 (s,3H), 1.43 (s,3H), 2.17 (m,1H), 2.30 (m,1H), 2.6-3.1 (m,5H), 3.22 (dd;3,12 Hz;1H), 3.86 (m,1H), 4.48 (dd;7,12 Hz;1H), 4.50 (d,12 Hz,1H), 4.70 (d,12 Hz,1H), 7.11 (d,8 Hz,1H), 7.15-7.45 (m,8H). FAB-MS: calculated for C25H33N3O3 423; found 424 (M+H, 100%).

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

Procedure: Prepared from 3-amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide, trifluoroacetate (Example 107, Step C) and (R)-2-benzyloxypropanol (prepared from ethyl-D-lactate according to the procedure of Hanessian and Kloss, Tetrahedron Lett. 1985, 26, 1261-1264.) by the procedure described in Example 86, Step A. 1H NMR (200 MHz,CD3OD): 1.31 (d,6 Hz,3H), 1.4 (s,3H), 1.43 (s,3H), 2.17 (m,1H), 2.30 (m,1H), 2.6-3.1 (m,5H), 3.22 (dd;3,12 Hz;1H), 3.86 (m,1H), 4.48 (dd;7,12 Hz;1H), 4.50 (d,12 Hz,1H), 4.70 (d,12 Hz,1H), 7.11 (d,8 Hz,1H), 7.15-7.45 (m,8H). FAB-MS: calculated for C25H33N3O3 423; found 424 (M+H, 100%).

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

Procedure: A mixture of 2,4,6-trichloro-pyrimidin-5-ol (600 mg, 3.01 mmol), (R)-2-hydroxy-propionic acid ethyl ester (411 μL, 3.60 mmol), triphenylphosphine (906 mg, 3.45 mmol) and DIAD (678 μL, 3.45 mmol) in dioxane (5 mL) was stirred at RT for 18 hours before being concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-25% ethyl acetate in cyclohexane) affording (R)-2-(2,4,6-Trichloro-pyrimidin-5-yloxy)-propionic acid ethyl ester (522 mg, 52%). 1H NMR (400 MHz, CDCl3): δ 4.30-4.16 (2H, m), 4.12 (1H, q, J=7.14 Hz), 1.70 (3H, d, J=6.78 Hz), 1.29 (3H, t, J=7.19 Hz). before being concentrated in vacuo The resulting residue was purified by column chromatography (SiO2, gradient 0-25% ethyl acetate in cyclohexane)

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.7 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-bromophenol (8.65 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (12.2 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.7 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-bromophenol (8.65 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (12.2 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.74 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-phenylphenol (8.51 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (11.3 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.74 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-phenylphenol (8.51 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (11.3 g). Prepared The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3)

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

Procedure: Prepared from 3-amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide, trifluoroacetate (Example 107, Step C) and (R)-2-benzyloxypropanal (prepared from ethyl-D-lactate according to the procedure of Hanessian and Kloss, Tetrahedron Lett. 1985, 26, 1261-1264.) by the procedure described in Example 86, Step A. 1H NMR (200 Mhz,CD3OD): 1.31 (d,6 Hz,3H), 1.40 (s,3H), 1.43 (s,3H), 2.17 (m,1H), 2.30 (m,1H), 2.6-3.1 (m,5H), 3.22 (dd;3,12 Hz;1H), 3.86 (m,1H), 4.48 (dd;7,12 Hz;1H), 4.50 (d,12 Hz,1H), 4.70 (d,12 Hz,1H), 7.11 (d,8 Hz,1H), 7.15-7.45 (m,8H). FAB-MS: calculated for C25H33N3O3 423; found 424 (M+H,100%).

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-ethyl 2-hydroxypropanoate (15 g, 0.127 mol) and TEA (15.4 g, 0.15 mol) were added to THF and then cooled to 10-15° C. Then MsCl (15 g, 0.13 mol) was added to the solution dropwise with cooling while maintaining the temperature in the range of 10-15° C. at about 2 hours. The mixture was allowed to warm to about 20° C. and the solid was filtered off. The solution was washed with water and dried, concentrated to afford (R)-ethyl 2-(methylsulfonyloxy)propanoate (15 g, 60%). 1H NMR (400 MHz, CDCl3) δ ppm, 5.11-5.14 (q, 1H), 4.24-4.29 (m, 2H), 2.81-3.17 (q, 3H, J=7.2 Hz), 1.61-1.43 (d, 3H, J=7.6 Hz), 1.30-1.32 (m, 3H). with cooling while maintaining the temperature in the range of 10-15° C. at about 2 hours to warm to about 20° C. the solid was filtered off The solution was washed with water dried concentrated

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

Procedure: Following General Procedure AM using Ethyl-D-lactate (Fluka) and N-[(1RS,2RS)-1,2,3,4-tetrahydro-1-hydroxy-2-naphthyl]-amine (Liebigs Ann. Chem. 1992, pp273, incorporated herein by reference), the title compound was prepared. C15H21NO3 (MW=263.335); mass spectroscopy (MH+) 264.