Thiophenol → (r)-2-(3-Chloro-4-(2-methoxyethyloxy)benzyl)morpholine

Participants

Reaction Conditions

Reaction Steps

N-BOC-(R)-2-(3-chloro-4-hydroxybenzyl)morpholine, example 7, intermediate (a) (52 mg, 0.16 mmol), was dissolved in acetone (1.5 mL) with potassium carbonate (44 mg, 0.32 mmol) and 2-bromoethylmethyl ether (44 uL, 0.47 mmol) added in one portion. The reaction was then heated to 55° C. and shaken at that temperature for 16 hrs. The reaction mixture was filtered, washing with acetone (1 mL×2) and the liquor evaporated under a high flow of nitrogen. The residue was dissolved in tetrahydrofuran: ethanol (1:1, 4 mL) and polymer supported thiophenol (0.43 g, 0.64 mmol), MP-carbonate (0.24 g, 0.64 mmol) and diisopropylethylamine (119 uL, 0.68 mmol) added. The reaction was shaken for 24 hrs, then filtered and concentrated under a high flow of nitrogen. The crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.0 mL) and shaken for 3 hrs at room temperature. The reaction mixture was added directly to an SCX-2 column (2 g) and washed with dichloromethane (2 mL×2) and methanol (2 mL×2). The SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL). Combined ammonia washes were concentrated in vacuo to yield the desired morpholine example 43 as a colorless oil (19 mg).

Provenance & Evidence