(2S)-2-methoxypropan-1-ol

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

Procedure: To a stirred solution of (S)-2-methoxypropan-1-ol (1.00 g, 11.1 mmol) in DCM (50 mL) was added Et3N (2.33 mL, 16.6 mmol). A solution of toluene sulfonyl chloride (2.54 g, 13.3 mmol) in DCM (20 mL) was added dropwise at 0° C. under nitrogen. The reaction mixture was allowed to warm to ambient temperature and was stirred overnight. The reaction was diluted with DCM, washed with saturated aqueous NaHCO3 and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 10:1 to 4:1) to give (S)-2-methoxypropyl 4-methylbenzenesulfonate (2.03 g, 75%). washed with saturated aqueous NaHCO3 and brine dried concentrated The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 10:1 to 4:1)

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

Procedure: To a stirred solution of 2-methylquinolin-7-ol (1.00 g, 6.28 mmol), PPh3 (4.12 g, 15.7 mmol) and (S)-2-methoxypropan-1-ol (0.679 g, 7.54 mmol) in THF (60 mL) was added dropwise diisopropyl azodicarboxylate (2.05 mL, 10.1 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at ambient temperature overnight. The reaction was then heated at 50° C. for additional 2 hours. After cooling, to the reaction were added 4N HCl (3.1 mL), water (100 mL) and EtOAc (200 mL). The aqueous layer was separated and washed with EtOAc (100 mL). The aqueous was neutralized with ammonium hydroxide to about pH 9, extracted with EtOAc, washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc) to give (S)-7-(2-methoxypropoxy)-2-methylquinoline (0.738 g, 51%). The reaction was then heated at 50° C. for additional 2 hours After cooling, to the reaction The aqueous layer was separated washed with EtOAc (100 mL) extracted with EtOAc washed with brine dried concentrated under reduced pressure The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described for Intermediate example I-81 in 67% yield starting from ethyl 6-chloronicotinate and (s)-(+)-2-methoxypropanol. The reduction was performed using 3 equiv of lithium hydroxide while heating to 75° C. for 3 h. The final aqueous solution was extracted with ethyl acetate in order to collect the product; 1H NMR (400 MHz, CD3OD) δ ppm 8.77 (d, 1 H), 8.21 (dd, 1 H), 6.87 (d, 1 H), 4.27-4.40 (m, 2 H), 3.69-3.81 (m, 1 H), 3.42 (s, 3 H), 1.24 (d, 3 H); MS (ESI) m/z 212[M+H+], m/z 210 [M−H+]. The final aqueous solution was extracted with ethyl acetate in order to collect the product

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

Procedure: By reduction of the (+)-(R)-2-methoxy-propionic acid known from the prior art with lithium aluminium hydride (LiAlH4) the (-)-(R)-2-methoxy-propanol is obtained with a boiling point of 70° C. under a pressure of 76 mbar and a specific rotation of [α]D25 =-15.8° (c=100). The corresponding (+)-(S)-2-methoxy-propanol with a boiling point of 70° C. under a pressure of 76 mbar and a rotation of [α]D25 =+16.5° (c=100) is obtained analogously from the equally well known (-)-(S)-2-methoxy-propionic acid. is obtained with a boiling point of 70° C. under a pressure of 76 mbar a specific rotation of [α]D25 =-15.8° (c=100)

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

Procedure: By reduction of the (+)-(R)-2-methoxy-propionic acid known from the prior art with lithium aluminium hydride (LiAlH4) the (-)-(R)-2-methoxy-propanol is obtained with a boiling point of 70° C. under a pressure of 76 mbar and a specific rotation of [α]D25 =-15.8° (c=100). The corresponding (+)-(S)-2-methoxy-propanol with a boiling point of 70° C. under a pressure of 76 mbar and a rotation of [α]D25 =+16.5° (c=100) is obtained analogously from the equally well known (-)-(S)-2-methoxy-propionic acid. is obtained with a boiling point of 70° C. under a pressure of 76 mbar a specific rotation of [α]D25 =-15.8° (c=100)

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

Procedure: To a stirred solution of (S)-2-methoxypropan-1-ol (1.00 g, 11.1 mmol) in DCM (50 mL) was added Et3N (2.33 mL, 16.6 mmol). A solution of toluene sulfonyl chloride (2.54 g, 13.3 mmol) in DCM (20 mL) was added dropwise at 0° C. under nitrogen. The reaction mixture was allowed to warm to ambient temperature and was stirred overnight. The reaction was diluted with DCM, washed with saturated aqueous NaHCO3 and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 10:1 to 4:1) to give (S)-2-methoxypropyl 4-methylbenzenesulfonate (2.03 g, 75%). washed with saturated aqueous NaHCO3 and brine dried concentrated The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 10:1 to 4:1)

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

Procedure: To a stirred solution of 2-methylquinolin-7-ol (1.00 g, 6.28 mmol), PPh3 (4.12 g, 15.7 mmol) and (S)-2-methoxypropan-1-ol (0.679 g, 7.54 mmol) in THF (60 mL) was added dropwise diisopropyl azodicarboxylate (2.05 mL, 10.1 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at ambient temperature overnight. The reaction was then heated at 50° C. for additional 2 hours. After cooling, to the reaction were added 4N HCl (3.1 mL), water (100 mL) and EtOAc (200 mL). The aqueous layer was separated and washed with EtOAc (100 mL). The aqueous was neutralized with ammonium hydroxide to about pH 9, extracted with EtOAc, washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc) to give (S)-7-(2-methoxypropoxy)-2-methylquinoline (0.738 g, 51%). The reaction was then heated at 50° C. for additional 2 hours After cooling, to the reaction The aqueous layer was separated washed with EtOAc (100 mL) extracted with EtOAc washed with brine dried concentrated under reduced pressure The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc)

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

Procedure: To a stirred solution of 2-methylquinolin-7-ol (1.00 g, 6.28 mmol), PPh3 (4.12 g, 15.7 mmol) and (S)-2-methoxypropan-1-ol (0.679 g, 7.54 mmol) in THF (60 mL) was added dropwise diisopropyl azodicarboxylate (2.05 mL, 10.1 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at ambient temperature overnight. The reaction was then heated at 50° C. for additional 2 hours. After cooling, to the reaction were added 4N HCl (3.1 mL), water (100 mL) and EtOAc (200 mL). The aqueous layer was separated and washed with EtOAc (100 mL). The aqueous was neutralized with ammonium hydroxide to about pH 9, extracted with EtOAc, washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc) to give (S)-7-(2-methoxypropoxy)-2-methylquinoline (0.738 g, 51%). The reaction was then heated at 50° C. for additional 2 hours After cooling, to the reaction The aqueous layer was separated washed with EtOAc (100 mL) extracted with EtOAc washed with brine dried concentrated under reduced pressure The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc)

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

Procedure: By reduction of the (+)-(R)-2-methoxy-propionic acid known from the prior art with lithium aluminium hydride (LiAlH4) the (-)-(R)-2-methoxy-propanol is obtained with a boiling point of 70° C. under a pressure of 76 mbar and a specific rotation of [α]D25 =-15.8° (c=100). The corresponding (+)-(S)-2-methoxy-propanol with a boiling point of 70° C. under a pressure of 76 mbar and a rotation of [α]D25 =+16.5° (c=100) is obtained analogously from the equally well known (-)-(S)-2-methoxy-propionic acid. is obtained with a boiling point of 70° C. under a pressure of 76 mbar a specific rotation of [α]D25 =-15.8° (c=100)

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

Procedure: By reduction of the (+)-(R)-2-methoxy-propionic acid known from the prior art with lithium aluminium hydride (LiAlH4) the (-)-(R)-2-methoxy-propanol is obtained with a boiling point of 70° C. under a pressure of 76 mbar and a specific rotation of [α]D25 =-15.8° (c=100). The corresponding (+)-(S)-2-methoxy-propanol with a boiling point of 70° C. under a pressure of 76 mbar and a rotation of [α]D25 =+16.5° (c=100) is obtained analogously from the equally well known (-)-(S)-2-methoxy-propionic acid. is obtained with a boiling point of 70° C. under a pressure of 76 mbar a specific rotation of [α]D25 =-15.8° (c=100)

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

Procedure: The title compound was synthesized in analogy to the procedure described for the preparation of Example 31, using 5-bromo-6-chloro-3-pyridinecarboxylic acid, (S)-(+)-2-methoxypropanol (commercially available), 4-chlorophenyl-boronic acid (commercially available), and (1R,2R)-2-amino-cyclohexanol (commercially available) as starting materials. MS (ISP): 419.2 (M+H+). described for the preparation of Example 31

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

Procedure: By reduction of the (+)-(R)-2-methoxy-propionic acid known from the prior art with lithium aluminium hydride (LiAlH4) the (-)-(R)-2-methoxy-propanol is obtained with a boiling point of 70° C. under a pressure of 76 mbar and a specific rotation of [α]D25 =-15.8° (c=100). The corresponding (+)-(S)-2-methoxy-propanol with a boiling point of 70° C. under a pressure of 76 mbar and a rotation of [α]D25 =+16.5° (c=100) is obtained analogously from the equally well known (-)-(S)-2-methoxy-propionic acid. is obtained with a boiling point of 70° C. under a pressure of 76 mbar a specific rotation of [α]D25 =-15.8° (c=100)