1-butylsulfanylbutane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a THF solution (0.5 M) of 2-bromopyridine (2.8 eq.) was added, at −78° C., n-butyl lithium (1.6 M hexane solution, 2.8 eq.) dropwise over 15 min. The resulting yellow suspension was stirred at −78° C. for a further 15 min before an ether solution (0.5 M) of cuprous iodide (1.4 eq.) and dibutyl sulfide (2.8 eq.) was added over 15 min. The resulting reaction mixture was allowed to stir at −78° C. for 15 min and then at 0° C. for 15 min. Finally, to this was added dropwise at 0° C., a THF solution (0.1 M) of (2E)-2-cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)acrylamide (Example 1, Step 2, 1 eq.). The resulting emerald green suspension was stirred at 0° C. for 15 min and then at RT for 2 h. The reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl:conc. aq. NH4OH solution and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude product thus obtained was purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc). The title compound was isolated as a mixture of diastereomers. was added over 15 min The resulting reaction mixture at 0° C. for 15 min Finally, to this was added dropwise at 0° C. The resulting emerald green suspension was stirred at 0° C. for 15 min at RT for 2 h The reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl aq. NH4OH solution and extracted with ether The combined organic extracts were washed with brine dried over MgSO4 filtered the filtrate concentrated in vacuo The crude product thus obtained was purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc)

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

Procedure: The di-n-butylmethylsulfonium iodide was prepared in situ starting from di-n-butylsulfide and methyl iodide. Di-n-butylmethylselenonium iodide was prepared in situ starting from di-n-butylselenide and methyl iodide.

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

Procedure: The di-n-butylmethylsulfonium iodide was prepared in situ starting from di-n-butylsulfide and methyl iodide. Di-n-butylmethylselenonium iodide was prepared in situ starting from di-n-butylselenide and methyl iodide.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of the compound of Example 1 (3.0 g, 4.2 mmol) and butyl sulfide (18 mL) in acetonitrile (24 mL) at 0° C. was added benzoyl peroxide (2.0 g) in three portions over 3 hours, and the reaction was stirred at 0° C. for 1 hour and then at room temperature for 1 hour. Additional benzoyl peroxide (4.0 g) was added in two portions over 2 hours at room temperature. The reaction was diluted with ethyl acetate and washed with 10% Na2CO3 and brine. The organic phase was dried over MgSO4, filtered and evaporated. The concentrate was chromatographed on silica gel eluting with a gradient starting with 50% ethyl acetate in chloroform and ending with ethyl acetate to give the title compound (2.43 g, 68% yield). at room temperature for 1 hour washed with 10% Na2CO3 and brine The organic phase was dried over MgSO4 filtered evaporated The concentrate was chromatographed on silica gel eluting with a gradient

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

Procedure: The general procedure was used to convert 4-iodo bromobenzene and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a clear oil (450 mg, 92% yield). 1H NMR (300 MHz, CDCl3) δ 7.39–7.36 (d, J=8.6, 2H; Ha, Ha′), 7.19–7.15 (d, J=8.28, 2H; Hb, Hb′), 2.91–2.86 (t, J=7.1, 2H; Hc), 1.57–1.47 (m, 2H; Hd), 1.41–1.31 (m, 2H; He), 0.94–0.89 (t, J=7.3, 3H; Hf). 13C NMR (75 MHz, CDCl3) δ 136.2 (C4), 131.7 (C1, C1′), 130.2 (C2, C2′), 119.2 (C3), 33.2 (C5), 30.9 (C6), 21.8 (C7), 13.5 (C8). Anal. Calcd. for C10H13Br C, 48.99; H, 5.34; S, 13.08; Found C, 49.09; H, 5.44; S, 12.96.

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

Procedure: The general procedure was used to convert 4-iodo bromobenzene and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a clear oil (450 mg, 92% yield). 1H NMR (300 MHz, CDCl3) δ 7.39–7.36 (d, J=8.6, 2H; Ha, Ha′), 7.19–7.15 (d, J=8.28, 2H; Hb, Hb′), 2.91–2.86 (t, J=7.1, 2H; Hc), 1.57–1.47 (m, 2H; Hd), 1.41–1.31 (m, 2H; He), 0.94–0.89 (t, J=7.3, 3H; Hf). 13C NMR (75 MHz, CDCl3) δ 136.2 (C4), 131.7 (C1, C1′), 130.2 (C2, C2′), 119.2 (C3), 33.2 (C5), 30.9 (C6), 21.8 (C7), 13.5 (C8). Anal. Calcd. for C10H13Br C, 48.99; H, 5.34; S, 13.08; Found C, 49.09; H, 5.44; S, 12.96.

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

Procedure: The general procedure was used to convert diiodobenzene and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a pale yellow oil (512 mg, 88% yield). 1H NMR (300 MHz, CDCl3) δ 7.58–7.55 (d, J=8.4, 2H; Ha, Ha′), 7.05–7.02 (d, J=8.2, 2H; Hb, Hb′), 2.91–2.86 (t, J=7.3, 2H; Hc), 1.67–1.49 (m, 2H; Hd), 1.42–1.30 (m, 2H; He), 0.94–0.89 (t, J=7.3, 3H; methyl protons). 13C NMR (75 MHz, CDCl3) δ 137.6 (C1, C1′), 137.2 (C4), 130.2 (C2, C2′), 90.0 (C3), 32.9 (C5), 30.9 (C6), 21.9 (C7), 13.6 (C8). High Resolution Mass. Spec. for C10H13S; Expected, 291.9783; Found, 291.9796

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

Procedure: The general procedure was used to convert 2-iodoanisole and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a light yellow oil (329 mg, 84% yield). 1H NMR (300 MHz, CDCl3) δ 7.18–6.75 (m, 4H; Hb, Hc, Hd, He); 3.82 (s, 3H; Hj), 2.84–2.79 (t, J=7.3, 2H; Hf), 1.60–1.52 (m, 2H; Hg), 1.43–1.36 (m, 2H; Hh) 0.87–0.82 (t, J=7.3, 3H; Hi). 13C NMR (75 MHz, CDCl3) δ 156.98 (C6), 128.56 (C2), 126.54 (C4), 125.22 (C1), 120.98 (C3), 110.28 (C5), 55.73 (C11), 31.49 (C7), 30.94 (C8), 22.06 (C9), 13.66 (C10). Anal. Calcd. for C11H160S: C, 67.30; H, 8.22; S, 16.33; Found C, 67.43; H, 8.28; S, 16.10.

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

Procedure: The general procedure was used to convert 2-iodoanisole and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a light yellow oil (329 mg, 84% yield). 1H NMR (300 MHz, CDCl3) δ 7.18–6.75 (m, 4H; Hb, Hc, Hd, He); 3.82 (s, 3H; Hj), 2.84–2.79 (t, J=7.3, 2H; Hf), 1.60–1.52 (m, 2H; Hg), 1.43–1.36 (m, 2H; Hh) 0.87–0.82 (t, J=7.3, 3H; Hi). 13C NMR (75 MHz, CDCl3) δ 156.98 (C6), 128.56 (C2), 126.54 (C4), 125.22 (C1), 120.98 (C3), 110.28 (C5), 55.73 (C11), 31.49 (C7), 30.94 (C8), 22.06 (C9), 13.66 (C10). Anal. Calcd. for C11H160S: C, 67.30; H, 8.22; S, 16.33; Found C, 67.43; H, 8.28; S, 16.10.

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

Procedure: The general procedure was used to convert 4-methoxy iodobenzene and n-butyl sulfide to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a clear oil (370 mg, 95% yield). 1H NMR (300 MHz, CDCl3) δ 7.26–7.23 (d, J=9.0. 2H; Hb, Hb′), 6.76–6.73 (d, J=8.8, 2H; Hc, Hc′), 3.69 (s, 3H; Hg), 2.75–2.70 (t, 2H; Hd), 1.50–1.43 (m, 2H; He), 1.36–1.28 (m, 2H; Hf), 0.83–0.78 (t, 3H; methyl protons). 13C NMR (75 MHz, CDCl3) δ 158.62 (C4), 132.81 (C1), 126.85 (C2, C2), 114.39 (C3, C3), 55.21 (C9), 35.04 (C5), 31.63 (C6), 21.75 (C7), 13.59 (C8). Anal. Calcd. for C11H16SO: C, 67.30; H, 8.22; S, 16.33; Found C, 66.87; H, 8.28; S, 16.21.