ethyl 3,4-dihydro-2H-chromene-2-carboxylate

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

Procedure: A solution of ethyl 2-chromanecarboxylate (1.575 g, 7.68 mmol) in a mixture of tetrahydrofuran (75 ml) and water (2 ml) was added with sodium borohydride (0.686 g, 18.2 mmol) in small portions and the mixture was left under stirring at room temperature for 48 h. Afterwards the mixture was cooled at -10° C. and added with acetone (47 ml) stirring at room temperature for 0.5 h. Subsequently water (100 ml) was added and the mixture was extracted with dichloromethane. The combined organic phases were dried and the solvent was removed by evaporation under reduced pressure, thereby obtaining 1.218 g of the title product (97% yield). the mixture was left Afterwards the mixture was cooled at -10° C. stirring at room temperature for 0.5 h the mixture was extracted with dichloromethane The combined organic phases were dried the solvent was removed by evaporation under reduced pressure

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

Procedure: A solution of ethyl 4-oxo-4H-1-benzopyran-2-carboxylate (2.0 g, 9.17 mmol) in methanol (60 ml), chloroform (25 ml) and glacial acetic acid (20 ml) was added with 10% palladium-on-charcoal and the mixture was left under stirring at room pressure and temperature for 24 h. under hydrogen atmosphere. After that, the catalyst was filtered off and the filtrate was evaporated to dryness. The residue was redissolved in ethyl ether and washed successively with a 5% sodium bicarbonate solution and a sodium chloride saturated solution. The mixture was dried and the solvent was evaporated off under reduced pressure, to obtain 1.575 g of the title product (84% yield). the mixture was left After that, the catalyst was filtered off the filtrate was evaporated to dryness The residue was redissolved in ethyl ether washed successively with a 5% sodium bicarbonate solution The mixture was dried the solvent was evaporated off under reduced pressure

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

Procedure: Chroman-2-carboxylic acid (35.6 g, 0.2 mol) prepared according to the method of Augstein et al., J. Med. Chem., v. 11, pp. 844-848, 1968) and absolute ethanol (24.3 g, 0.6 mol) were combined in 300 ml of CH2Cl2. H2SO4 (0.6 ml, 96%) was added and the mixture gently refluxed for 21 hours, then cooled and diluted with 500 ml H2O. The organic layer was separated, washed with saturated NaHCO3 and then H2O, dried (MgSO4) and stripped to yield present title product as an oil; 38.6 g (93%); 1H-NMR (CDCl3), 300 MHz) delta 7.12 (t, 1H), 7.02 (d, 1H), 6.92 (d, 1H), 6.85 (t, 1H), 4.71 (q, 1H), 4.25 (q. 2H), 2.80 (m, 2H), 2.22 (m, 2H), 1.29 (t, 3H). the mixture gently refluxed for 21 hours cooled The organic layer was separated washed with saturated NaHCO3 H2O, dried (MgSO4)