(1S)-1-(4-fluorophenyl)ethanol

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

Procedure: To a stirred suspension of sodium hydride (3.14 g, 55% dispersion in oil) in dry DMF (180 ml) under an argon atmosphere was added (S)-1-(4-fluorophenyl)-ethanol (8.41 g, CAS 101219-73-2). Allyl bromide (6.6 ml) was then added dropwise. The reaction mixture was stirred for 30 min at room temperature and was then quenched by addition of water. The mixture was extracted with ethyl acetate twice. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give 1-((S)-1-allyloxy-ethyl)-4-fluoro-benzene (8.66 g, 80%) as a colourless liquid. 1H NMR (300 MHz, CDCl3, δ ppm): 1.43 (d, J=6.6 Hz, 3H), 3.84 (m, 2H), 4.45 (q, J=6.6 Hz, 1H), 5.15 (dd, J1=10.5 Hz, J2=1.8 Hz, 1H), 5.22 (dd, J1=17.4 Hz, J2=1.8 Hz, 1H), 5.89 (m, 1H), 7.03 (m, 2H), 7.29 (m, 2H). was then quenched by addition of water The mixture was extracted with ethyl acetate twice The combined organic layers were dried (MgSO4) concentrated in vacuo The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

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

Procedure: To a stirred suspension of sodium hydride (3.14 g, 55% dispersion in oil) in dry DMF (180 ml) under an argon atmosphere was added (S)-1-(4-fluorophenyl)-ethanol (8.41 g, CAS 101219-73-2). Allyl bromide (6.6 ml) was then added dropwise. The reaction mixture was stirred for 30 min at room temperature and was then quenched by addition of water. The mixture was extracted with ethyl acetate twice. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give 1-((S)-1-allyloxy-ethyl)-4-fluoro-benzene (8.66 g, 80%) as a colourless liquid. 1H NMR (300 MHz, CDCl3, δ ppm): 1.43 (d, J=6.6 Hz, 3H), 3.84 (m, 2H), 4.45 (q, J=6.6 Hz, 1H), 5.15 (dd, J1=10.5 Hz, J2=1.8 Hz, 1H), 5.22 (dd, J1=17.4 Hz, J2=1.8 Hz, 1H), 5.89 (m, 1H), 7.03 (m, 2H), 7.29 (m, 2H). was then quenched by addition of water The mixture was extracted with ethyl acetate twice The combined organic layers were dried (MgSO4) concentrated in vacuo The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

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

Procedure: To a stirred suspension of sodium hydride (3.14 g, 55% dispersion in oil) in dry DMF (180 ml) under an argon atmosphere was added (S)-1-(4-fluorophenyl)-ethanol (8.41 g, CAS 101219-73-2). Allyl bromide (6.6 ml) was then added dropwise. The reaction mixture was stirred for 30 min at room temperature and was then quenched by addition of water. The mixture was extracted with ethyl acetate twice. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give 1-((S)-1-allyloxy-ethyl)-4-fluoro-benzene (8.66 g, 80%) as a colourless liquid. 1H NMR (300 MHz, CDCl3, δ ppm): 1.43 (d, J=6.6 Hz, 3H), 3.84 (m, 2H), 4.45 (q, J=6.6 Hz, 1H), 5.15 (dd, J1=10.5 Hz, J2=1.8 Hz, 1H), 5.22 (dd, J1=17.4 Hz, J2=1.8 Hz, 1H), 5.89 (m, 1H), 7.03 (m, 2H), 7.29 (m, 2H). was then quenched by addition of water The mixture was extracted with ethyl acetate twice The combined organic layers were dried (MgSO4) concentrated in vacuo The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of methyl 6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (117 mg, 0.417 mmol) (Example 1, Step F) and triphenylphosphine (175 mg, 0.668 mmol) in tetrahydrofuran (THF) (3960 μl) under N2 was treated with (S)-1-(4-fluorophenyl)ethanol (84 μl, 0.668 mmol), heated to 65° C., and treated with DIAD (130 μl, 0.668 mmol). After stirring for 30 min, the reaction was cooled to rt, then concentrated. Purification with column chromatography (0-100% EtOAc/Hexane) afforded (R)-methyl 1-(1-(4-fluorophenyl)ethyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (18.6 mg, 0.046 mmol, 11.07% yield) as pale yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.37 (d, J=8.1 Hz, 2 H), 7.32-7.18 (m, 4 H), 7.14 (d, J=3.7 Hz, 1 H), 7.03-6.94 (m, 2 H), 6.40-6.28 (m, 2 H), 3.62 (s, 3 H), 2.68 (s, 3 H), 2.41 (s, 3 H), 1.88 (d, J=7.2 Hz, 3 H); LCMS (m/z) ES+=403 (M+1). the reaction was cooled to rt concentrated Purification with column chromatography (0-100% EtOAc/Hexane)