(2-(Dimethylamino)ethyl)triphenylphosphonium bromide → N,N-dimethyl-N-((2Z)-3-{3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}prop-2-enyl)amine

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Reaction Steps

To a suspension of [2-(dimethylamino)ethyl](triphenyl)phosphonium bromide (32.1 g, 77.4 mmol) in dry THF (150 mL) was added a solution of potassium tert-butoxide (9.4 g, 83.7 mmol) in dry t-BuOH (100 mL). The suspension was sonicated for 15 minutes whereafter a solution of 3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine-2-carbaldehyde (from Step 1; 18.3 g, 72.8 mmol) in THF (30 mL) was added to the yellow suspension and stirred at room temperature for one hour and then for a further hour at 60° C. The solvent was removed under reduced pressure and the residue was mixed with water (0.8 L) and the pH was adjusted to 3–4 with HOAc (˜10 mL) and then extracted twice with CHCl3. The aqueous phase was made basic and extracted with CHCl3 (×3), the combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product, consisting of the cis and trans* isomers were separated with preparative HPLC on an YMC ODS-AQ column (30×250 mm) with different gradients of 0.1% TFA in water/CH3CN. The cis isomer was isolated as a light yellow oil (2.33 g, 10%). HRMS m/z calcd for C17H26N2O3 (M)+ 306.1943. found 306.1942. *The corresponding trans isomer is described in Example 21, Step 1.

Provenance & Evidence