(2R)-1-phenylmethoxypropan-2-ol

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

Procedure: A mixture of Intermediate 95a (0.50 g, 2.2 mmol) in dry THF (17 mL) was treated with triphenylphosphine (1.13 g, 4.32 mmol) and (R)-(−)-1-benzyloxy-2-propanol (0.52 mL, 3.24 mmol) then diisopropylazodicarboxylate (0.85 mL, 4.32 mmol) was added dropwise (the reaction mixture became very warm). After stirring at ambient temperature for 1.75 h the mixture was treated with water (0.2 mL) then concentrated in vacuo to a viscous orange oil. The oil was purified by FCC, using 0-7% EtOAc in DCM. The resulting oil was purified further by FCC, using 0-30% EtOAc in cyclohexane. The product was applied to a pre-conditioned (with MeOH)SCX-2 cartridge and eluted with MeOH then 2N NH3 in MeOH. The product containing fractions were combined and concentrated in vacuo to give the title compound as a viscous golden oil (0.39 g, 48%). LCMS (Method 3): Rt 3.77 min, m/z 380.4 [MH+]. became very warm) then concentrated in vacuo to a viscous orange oil The oil was purified by FCC The resulting oil was purified further by FCC eluted with MeOH The product containing fractions concentrated in vacuo

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

Procedure: A mixture of Intermediate 95a (0.50 g, 2.2 mmol) in dry THF (17 mL) was treated with triphenylphosphine (1.13 g, 4.32 mmol) and (R)-(−)-1-benzyloxy-2-propanol (0.52 mL, 3.24 mmol) then diisopropylazodicarboxylate (0.85 mL, 4.32 mmol) was added dropwise (the reaction mixture became very warm). After stirring at ambient temperature for 1.75 h the mixture was treated with water (0.2 mL) then concentrated in vacuo to a viscous orange oil. The oil was purified by FCC, using 0-7% EtOAc in DCM. The resulting oil was purified further by FCC, using 0-30% EtOAc in cyclohexane. The product was applied to a pre-conditioned (with MeOH)SCX-2 cartridge and eluted with MeOH then 2N NH3 in MeOH. The product containing fractions were combined and concentrated in vacuo to give the title compound as a viscous golden oil (0.39 g, 48%). LCMS (Method 3): Rt 3.77 min, m/z 380.4 [MH+]. became very warm) then concentrated in vacuo to a viscous orange oil The oil was purified by FCC The resulting oil was purified further by FCC eluted with MeOH The product containing fractions concentrated in vacuo

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

Procedure: A mixture of Intermediate 95a (0.50 g, 2.2 mmol) in dry THF (17 mL) was treated with triphenylphosphine (1.13 g, 4.32 mmol) and (R)-(−)-1-benzyloxy-2-propanol (0.52 mL, 3.24 mmol) then diisopropylazodicarboxylate (0.85 mL, 4.32 mmol) was added dropwise (the reaction mixture became very warm). After stirring at ambient temperature for 1.75 h the mixture was treated with water (0.2 mL) then concentrated in vacuo to a viscous orange oil. The oil was purified by FCC, using 0-7% EtOAc in DCM. The resulting oil was purified further by FCC, using 0-30% EtOAc in cyclohexane. The product was applied to a pre-conditioned (with MeOH)SCX-2 cartridge and eluted with MeOH then 2N NH3 in MeOH. The product containing fractions were combined and concentrated in vacuo to give the title compound as a viscous golden oil (0.39 g, 48%). LCMS (Method 3): Rt 3.77 min, m/z 380.4 [MH+]. became very warm) then concentrated in vacuo to a viscous orange oil The oil was purified by FCC The resulting oil was purified further by FCC eluted with MeOH The product containing fractions concentrated in vacuo

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

Procedure: To a stirred solution of (R)-1-(benzyloxy)propan-2-ol (2.0 g, 12 mmol) in dry DMF (5 mL) was added NaH (1.5 g, 36 mmol) at 0 Celsius. The reaction mixture was then stirred for 30 min before adding 3-bromo-2-chloropyridine (2.3 g, 12 mmol) and stirring continued for another 4 h. The reaction was quenched by slow addition of water (10 mL) and the resultant mixture extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, concentrated to dryness, and the crude product purified by FCC to provide the title compound. stirring continued for another 4 h The reaction was quenched by slow addition of water (10 mL) the resultant mixture extracted with ethyl acetate (3×10 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated to dryness the crude product purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (60 wt % dispersion in mineral oil) (1380 mg, 34.6 mmol) in tetrahydrofuran (100 mL) cooled to 0° C. was added (2R)-1-benzyloxypropan-2-ol (5.00 g, 30.1 mmol) dropwise. The solution was stirred at 0° C. for 1 h then 1-methylprop-2-ynyl methanesulfonate (4780 mg, 32.3 mmol) was added dropwise and the reaction mixture was allowed to warm to room temp and stirred overnight. The reaction mixture was quenched by the addition of sat. aq. ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was adsorbed onto silica and purified by column chromatography (0-20% EtOAc in Heptane) to afford the title compound as a yellow oil (2.36 g, 36%, mixture of diastereomers). to warm to room temp stirred overnight The reaction mixture was quenched by the addition of sat. aq. ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over sodium sulfate filtered concentrated in vacuo purified by column chromatography (0-20% EtOAc in Heptane)

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

Procedure: (2R)-2-tetrahydropyranyloxy-1-hydroxypropane (60 g, 0.37 mol) was dropwise added to a suspension of sodium hydride (60%) (22 g) in THF (100 ml) under ice cooling. After completion of the dropwise addition, a solution of benzyl bromide (70 g) in DMF (300 ml) was dropwise added, followed by agitating the mixture at room temperature for 6 hours, pouring it into water (500 ml), extracting with toluene (300 ml), washing the resulting organic layer with water, concentrating it, dissolving the concentrate in ethanol (300 ml), adding 6N-hydrochloric acid (20 ml), agitating the mixture at 20° C. for 2 hours, distilling off ethanol, adding toluene (300 ml), washing the resulting organic layer with an alkali and then with water and distilling it under reduced pressure to obtain (R)-1-benzyloxy-2-propanol (b.p. 105°-107° C./5 mmHg) (28 g). After completion of the dropwise addition extracting with toluene (300 ml) washing the resulting organic layer with water concentrating it dissolving the concentrate in ethanol (300 ml) adding 6N-hydrochloric acid (20 ml) agitating the mixture at 20° C. for 2 hours distilling off ethanol adding toluene (300 ml) washing the resulting organic layer with an alkali and then with water distilling it under reduced pressure