N,N-dimethyl-2-phenylmethoxyacetamide

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

Procedure: Adapting procedures or variations thereof according to Benington et al., J. Org. Chem. 1961, 26, 194-197; and Griffiths et al., Tetrahedron, 1997, 53(52), 17815-17822, a 250 mL round-bottomed flask equipped with a magnetic stirring bar and rubber septum was charged with 1.22 mL (1.41 g, 8.51 mmol) of 2-(phenylmethoxy)acetic acid. The acid was dissolved in 30 mL of anhydrous dichloromethane (DCM). To the solution was added 1.86 g (9.0 mmol) of dicyclohexylcarbodiimide (DCC) and the reaction mixture was stirred for two hours at room temperature. Twenty (20) mL (40 mmol) of a two molar (2 M) solution of dimethyl amine (Me2NH) in tetrahydrofuran was added and the mixture stirred overnight at room temperature. The precipitated dicyclohexyl urea (DCU) was filtered off and the solvents removed under reduced pressure using a rotary evaporator. The residue was diluted with ethyl acetate (EtOAc) and the solution filtered again to remove residual DCU. The solution was washed successively with one molar (1.0 M) hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate (NaHCO3), brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvent removed under reduced pressure using a rotary evaporator to yield a brown solid. Final purification by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) as eluent (EtOAc/Hxn=1:9) provided 1.08 g (65% yield) of the title compound (36a). Rf=0.30 (EtOAc/Hxn=1:9). 1H NMR (400 MHz, CDCl3): δ=2.97 (s, 3H), 2.99 (s, 3H), 4.18 (s, 2H), 4.62 (s, 2H), 7.28-7.37 (m, 5H) ppm. MS (ESI) m/z: 194.1 (M+H)+, 216.1 (M+Na)+. The analytical data was consistent with the proposed structure and the data in the literature. and Griffiths et al., Tetrahedron, 1997, 53(52), 17815-17822, a 250 mL round-bottomed flask equipped with a magnetic stirring bar the mixture stirred overnight at room temperature The precipitated dicyclohexyl urea (DCU) was filtered off the solvents removed under reduced pressure a rotary evaporator The residue was diluted with ethyl acetate (EtOAc) the solution filtered again to remove residual DCU The solution was washed successively with one molar (1.0 M) hydrochloric acid a saturated aqueous solution of sodium hydrogen carbonate (NaHCO3), brine, dried over anhydrous magnesium sulfate (MgSO4) filtered the solvent removed under reduced pressure a rotary evaporator to yield a brown solid Final purification by silica gel column chromatography a mixture of ethyl acetate (EtOAc) and hexane (Hxn) as eluent (EtOAc/Hxn=1:9)