1-bromo-3-ethoxypropane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a Grignard reagent solution prepared from 3-ethoxypropyl bromide (41.7 g), magnesium metal (shoot, 11.2 g) and iodine (0.2 g) in 110 ml of anhydrous ether and 30 ml of anhydrous benzene, a solution of cis-1,3-dibenzyl-hexahydrothieno[3,4-d]imidazole-2,4-dione ([α]D20 + 91°, 60.0 g) in 700 ml of anhydrous benzene is added with stirring for two and half hours at 25° to 40°C. The mixture is stirred and refluxed at 68° to 73° C for 5 hours. The reaction mixture is decomposed by the addition of 3N sulfuric acid (280 g) below 20°C. The organic layer is washed with water and concentrated in vacuo to give the residual oil of 76 g of cis-1,3-dibenzyl-4-hydroxy-4-(3-ethoxypropyl)-hexahydrothieno[3,4-d]imidazol-2-one. [α]D20 + 17° (C = 1 in CHCl3). IR (Nujol) 3350 cm-1 (OH); 1690 cm-1 (C = O). The mixture is stirred refluxed at 68° to 73° C for 5 hours The organic layer is washed with water concentrated in vacuo

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

Procedure: 0.5 g (1.5 mmol) of N-[2,2-dimethyl-6-hydroxychroman-4-yl]-N-(2-methoxyethyl)methanesulfonamide (Example 16b) was reacted with potassium carbonate and 3-ethoxy-1-bromopropane analogously to Example 1g. After column chromatography on silica gel using n-heptane/EA (5:1), 0.35 g of oily product was obtained.

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

Procedure: 0.5 g (1.5 mmol) of N-[2,2-dimethyl-6-hydroxychroman-4-yl]-N-(2-methoxyethyl)methanesulfonamide (Example 16b) was reacted with potassium carbonate and 3-ethoxy-1-bromopropane analogously to Example 1g. After column chromatography on silica gel using n-heptane/EA (5:1), 0.35 g of oily product was obtained.

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.5 g (5 mmol) of N-[2,2-dimethyl-6-hydroxychroman-4-yl]-N-ethyl-methanesulfonamide were heated to 80° C. for 30 min with 1.38 g (10 mmol) of powdered potassium carbonate in 60 ml of DMA. 4 ml of 3-ethoxy-1-bromopropane were then added dropwise at 50-60° C., the mixture was heated to 110° C. for 2 h and concentrated in vac. after cooling, the residue was treated with water and aqueous hydrochloric acid, the mixture was extracted with EA, the organic phase was dried and concentrated, and the oily residue was chromatographed on silica gel using n-heptane/EA (2:1). 0.9 g of N-[6-(3-ethoxypropoxy)-2,2-dimethylchroman-4-yl]-N-ethyl-methanesulfonamide was crystallized from appropriate fractions using petroleum ether, m.p. 72-74° C. concentrated in vac after cooling the residue was treated with water and aqueous hydrochloric acid the mixture was extracted with EA the organic phase was dried concentrated the oily residue was chromatographed on silica gel 0.9 g of N-[6-(3-ethoxypropoxy)-2,2-dimethylchroman-4-yl]-N-ethyl-methanesulfonamide was crystallized from appropriate fractions

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

Procedure: 3-Ethoxypropyl bromide (7.5 g., 0.045 mole) is converted to the Grignard reagent using standard procedures (see above). To this solution (ca 60 ml.), stirred in an ice bath, is added dropwise a solution of 10 g. (0.030 mole) of 3-iodo-5H-dibenzo[a,d]cyclohepten-5-one in 30 ml. of dry THF. The mixture is stirred for 5 minutes and concentrated in vacuo. The residue is treated with saturated ammonium chloride solution and extracted three times with ether. The ether layer is washed once with water, dried over sodium sulfate, and evaporated in vacuo to an orange solid, m.p. 95°-105° (12.0 g., 95%). is added dropwise a solution of 10 g The mixture is stirred for 5 minutes concentrated in vacuo The residue is treated with saturated ammonium chloride solution extracted three times with ether The ether layer is washed once with water dried over sodium sulfate evaporated in vacuo to an orange solid, m.p. 95°-105° (12.0 g., 95%)

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

Procedure: Magnesium turnings (6.2 g., 0.255 mole) covered with dry tetrahydrofuran (30 ml.) in carefully-dried apparatus are treated with a solution of 3-ethoxypropylbromide (42.5 g., 0.255 mole) added dropwise to maintain reflux. After preparation of the Grignard reagent according to standard procedures, the mixture is cooled, and 16 g. (0.072 mole) of 3-amino-5H-dibenzo[a,d]cyclohepten-5-one added in portions over 5 minutes. The reaction is stirred 15 minutes, then poured into 200 ml. of saturated aqueous ammonium chloride. The layers are separated, and the aqueous layer extracted once with ether. The ether layer, combined with the original organic phase, is washed once with water, dried over sodium sulfate, and evaporated in vacuo to give the title compound in essentially quantitative yield. added dropwise to maintain reflux the mixture is cooled poured into 200 ml The layers are separated the aqueous layer extracted once with ether is washed once with water dried over sodium sulfate evaporated in vacuo

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

Procedure: 3-Ethoxypropyl bromide (7.5 g., 0.045 mole) is converted to the Grignard reagent using standard procedures (see above). To this solution (ca 60 ml.), stirred in an ice bath, is added dropwise a solution of 10 g. (0.030 mole) of 3-iodo-5H-dibenzo[a,d]cyclohepten-5-one in 30 ml. of dry THF. The mixture is stirred for 5 minutes and concentrated in vacuo. The residue is treated with saturated ammonium chloride solution and extracted three times with ether. The ether layer is washed once with water, dried over sodium sulfate, and evaporated in vacuo to an orange solid, m.p. 95°-105° (12.0 g., 95%). is added dropwise a solution of 10 g The mixture is stirred for 5 minutes concentrated in vacuo The residue is treated with saturated ammonium chloride solution extracted three times with ether The ether layer is washed once with water dried over sodium sulfate evaporated in vacuo to an orange solid, m.p. 95°-105° (12.0 g., 95%)

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

Procedure: Magnesium turnings (6.2 g., 0.255 mole) covered with dry tetrahydrofuran (30 ml.) in carefully-dried apparatus are treated with a solution of 3-ethoxypropylbromide (42.5 g., 0.255 mole) added dropwise to maintain reflux. After preparation of the Grignard reagent according to standard procedures, the mixture is cooled, and 16 g. (0.072 mole) of 3-amino-5H-dibenzo[a,d]cyclohepten-5-one added in portions over 5 minutes. The reaction is stirred 15 minutes, then poured into 200 ml. of saturated aqueous ammonium chloride. The layers are separated, and the aqueous layer extracted once with ether. The ether layer, combined with the original organic phase, is washed once with water, dried over sodium sulfate, and evaporated in vacuo to give the title compound in essentially quantitative yield. added dropwise to maintain reflux the mixture is cooled poured into 200 ml The layers are separated the aqueous layer extracted once with ether is washed once with water dried over sodium sulfate evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir: