Wittig

Examples:

Example 1

To a suspension of methyl triphenylphosphonium bromide (2.4 g, 6.6 mmol) in THF was added tBuOK (1M in THF, 7.1 mmol) at RT. After stirring for 90 min, a solution of the SM (1.25 g, 3.35 mmol) in dry THF was added. The resulting mixture was stirred at RT for 18 h, after which time it was partitioned between saturated NH4Cl and MTBE. The org layer was dried (Na2SO4), concentrated, and purified by flash chromatography (25-30% EtOAc/hexane) to provide the product as a colorless oil. [0.3 g, 24%] [UK Pat App GB2463151A, page 141]

Example 2

To a solution of the SM (607 g, 1.570 mol) and methyl triphenylphosphonium bromide (673 g, 1.884 mol) in THF (1.000 L) was added tBuOK (1.0M in THF, 1.884 L, 1.884 mol) via addition funnel over 2 h. The reaction mixture was stirred at RT for 16 h, after which time it was concentrated to remove most THF. The resulting mixture was suspended in hexanes, passed through a pad of silica gel (1 Kg), eluting with hexanes (8 L), then 10% EtOAc/hexane (4 L). The mixture was concentrated to provide the product. [600 g, 99%] [WO2010045258, page 80]

Example 3

To a solution of the SM (5.22 g, 29.0 mmol) in methyl triphenylphosphonium bromide (12.4 g, 34.8 mmol) in THF (100 mL) was added tBuOK (1.0M in THF, 34.8 mL, 34.8 mmol) via addition funnel over 15 min. The resulting mixture was stirred at RT for 30 min. The mixture was filtered and the filtrate concentrated. The resulting material was purified by chromatography to provide the product as a solid. [3.85 g, 74.6%] [WO2010045258, page 82]

Example 4

n-BuLi (2.6M in hexane, 2.3 mL, 5.94 mmol) was added dropwise to a stirred solution of (methoxymethyl)triphenylphosphonium chloride (2.04 g, 5.94 mmol) in THF (20 mL) at -78 C. The mixture was stirred at -78 C for 10 min then at RT for 2.5 h. The mixture was cooled again to -78 C and was treated slowly with a solution of the SM (500 mg, 3.96 mmol) in THF (5 mL). The reaction mixture was allowed to warm to RT and stir O/N. The mixture was quenched with sat aq NaHCO3 (20 mL) and extracted with EtOAc. The combined organics were dried (Na2SO4) and concentrated to provide the product as a pale yellow oil which was used for the next step without further purification. [512 mg, crude] [WO2015129926, page 71]

Example 5

LiHMDS (1.0 M in THF, 15 mL, 15 mmol) was added dropwise to a solution of methyl triphenylphosphonium bromide (5.36 g, 15 mmol) in THF (50 mL) at 0 C. The mixture was stirred at 0 C for 40 min. A solution of the SM (2.04 g, 12 mmol) in THF (20 mL) was then added slowly at 0 C. The reaction mixture was stirred at 0 C to RT for 2 h. The mixture was quenched with sat aq NH4Cl and extracted with hexane. The combined organics were dried (MgSO4) and concentrated in vacuo. The resulting material was suspended in 5:1 hexane/ether (100 mL) and filtered. The filtrate was concentrated in vacuo and the resulting residue was purified by silica gel chromatography (5% EtOAc/hexane) to provide the product as a colorless oil. [1.478 g, 73%] [WO2015129926, page 102]