Dichloromethane → 2-(4-bromophenethoxy)tetrahydro-2H-pyran

Participants

Reaction Steps

Into 30 mL of CH2Cl2 in a 150 mL RB flask was dissolved 4-bromophenethyl alcohol (7.00 g, 34.80 mmol) and 3,4-dihydro-2H-pyran (3.80 mL, 41.61 mmol). To this solution was added a few crystals of p-toluenesulfonic acid monohydrate. The reaction mixture was then stirred at room temperature under a blanket of nitrogen overnight. Overnight the reaction mixture changed colour again to a deep brown colour. The reaction mixture was transferred to a 250 mL separating funnel and extracted with 150 mL of saturated NaHCO3(aq) solution during which time the brown colouration in the organic layer faded to an orange colour. The layers were separated and the organic layer was extracted again with 150 mL of brine. The organic layer was then separated and dried over anhydrous MgSO4 for 1 hour at room temperature. The mixture was then filtered and the collected solid washed with 3×30 mL portions of CH2Cl2. The filtrate and washings were combined and stripped to dryness on a rotary evaporator to yield an orange oil. Column chromatographic conditions for the remainder of the crude product were determined by TLC analysis (10% EtOAc/90% n-hexane eluant) which indicated a major spot at Rf 0.5 with a few minor spots on and around the baseline. The crude product was then purified by dry column flash chromatography using a sinter of 80 mm diameter and 80 mm depth packed to a depth of 5.5 cm with Merck 60 (15-40 μm) silica gel, time per fraction: 4.00 minutes, crude product pre-loaded onto 12.5 g of Merck 60 (15-40 □m) and this loaded on top of the column. n-Hexane/EtOAc elution in 100 mL fractions with the EtOAc component increasing in 1% increments from 0% (fraction 1) to 15% (fraction 16). Fractions' 9 & 10 “foamed” on leaving the column and TLC (10% EtOAc/90% n-hexane) of fractions' 8-15 indicated pure product was contained in fractions' 9-12 and these were combined and stripped to dryness on a rotary evaporator before being further dried in vacuo (oil immersion pump) overnight at room temperature. Yield: 9.821 g (98.9%, colourless liquid). 1H NMR (CDCl3) δ 1.40-1.88 (m, 6H, [3×—CH2—]pyran), 2.86 (t, 2H, ArCH2—), 3.45 (m, 1H, [OCHaHb-]pyran), 3.58 (q, 1H, —OpyranCHaHb—), 3.73 (m, 1H, [OCHaHb-]pyran), 3.92 (q, 1H, —OpyranCHaHb—), 4.57 (m, 1H, [—OCHO-]pyran), 7.10 (d, 2H, ArH), 7.40 (d, 2H, ArH).

Provenance & Evidence