(3-chloro-2-hydroxypropyl) acetate

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:

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Epichlorohydrin (92.5 g, 1.0 mol) was dissolved in 61.2 g (1.0 mol) of glacial acetic acid and 0.35 g of ferric chloride was added. The mixture was stirred at 65° C. overnight. Another 0.35 g of ferric chloride was added and the mixture was stirred another day. It was then concentrated by evaporation under reduced pressure to obtain 153 g 3-chloro-2-hydroxypropyl acetate as an oil. A few crystals of p-toluenesulfonic acid were added and then 81.5 g (1.13 mol) of ethyl vinyl ether was added dropwise with stirring and cooling with an ice bath to keep the temperature below about 35° C. When the addition was complete, the mixture was stirred overnight at 40° C. The dark oily product was presumed to be 3-chloro-2-(1-ethoxyethoxy)propyl acetate. This oil was added dropwise with stirring to a mixture of 110 g (2.75 mol) of sodium hydroxide in 110 mL of water heated to 105° C. When the addition was complete, the mixture was heated at 105° C. with stirring for 4 hours. It was then cooled and poured into 500 mL of water. The resulting mixture was extracted with 2×500 mL of diethyl ether and the ethereal extract was washed with concentrated aqueous sodium chloride, dried over sodium sulfate, and concentrated by evaporation under reduced pressure at 30° C. to obtain a dark oil. This oil was distilled at 5 mm Hg (665 pascals) pressure. The 40 g portion boiling at 60-68° C., which was 3-(1-ethoxyethoxy)oxetane, was collected. This fraction was dissolved in 100 mL of methanol and 25 mg of p-toluenesulfonic acid was added with stirring at about 10° C. The mixture was stirred for 2 hours at ambient temperature and then 1.0 g of solid sodium bicarbonate was added with stirring. After 5 min, the mixture was filtered and concentrated by evaporation under reduce pressure. The colorless oil residue was distilled at 5 mm Hg (665 pascals) pressure and the 1.9 g fraction boiling at 50-56° C., which was the title compound, a colorless liquid, was collected. the mixture was stirred another day It was then concentrated by evaporation under reduced pressure

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

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

Procedure: 1-hydroxy-2-(tetrahydropyran-2-yl)oxy-3-chloropropane can be prepared by the following scheme: epichlorohydrin is reacted with acetic acid in the presence of a catalytic amount of iron trichloride to give a mixture of 1-acetyloxy-3-chloropropan-2-ol and 2-acetyloxy-3-chloropropan-1-ol, the major component. The mixture is treated with dihydropyran in the presence of p-toluenesulfonic acid for five hours at 25° C. to give a mixture of 1-acetyloxy-2-(tetrahydropyran-2-yl)oxy-3-chloropropane and 1-(tetrahydropyranyloxy)-2-acetyloxy-3-chloropropane. The mixture is added to a rapidly stirred mixture of aqueous methanol and potassium carbonate at 25° C. and stirred for two hours. Evaporation of the methanol, extraction and drying yields a mixture 1-hydroxy-2-(tetrahydropyran-2-yl)oxy-3-chloropropane and 1-(tetrahydropyran-2-yl)oxy-2-hydroxy-3-chloropropane. Fractional vacuum distillation yields pure 1-hydroxy-2-(tetrahydropyran-2-yl)-oxy-3-chloro-propane since the minor impurity is converted into the more volatile epoxy compound during the distillation procedure. to give to give Evaporation of the methanol, extraction drying

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

Procedure: To the crude acetate prepared in Example 8 was added 10 g of p-toluenesulfonic acid monohydrate and then dropwise, over a period of 2 hours, 815 g (11.3 moles) of ethyl vinyl ether. The reaction was midly exothermic and the temperature was maintained at 35°-37° C. by occasional cooling. After the addition was complete, the reaction mixture was heated at 35°-40° C. for 16 hours. The crude material was used in the subsequent step. the temperature was maintained at 35°-37° C. by occasional cooling After the addition the reaction mixture was heated at 35°-40° C. for 16 hours

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

Procedure: To the crude acetate prepared in Example 8 was added 10 g of p-toluenesulfonic acid monohydrate and then dropwise, over a period of 2 hours, 815 g (11.3 moles) of ethyl vinyl ether. The reaction was midly exothermic and the temperature was maintained at 35°-37° C. by occasional cooling. After the addition was complete, the reaction mixture was heated at 35°-40° C. for 16 hours. The crude material was used in the subsequent step. the temperature was maintained at 35°-37° C. by occasional cooling After the addition the reaction mixture was heated at 35°-40° C. for 16 hours

Conditions: temp:28.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1.5 g of anhydrous ferric chloride in 612 g (10.02 moles) of glacial acetic acid was added 925 g (10.0 moles) of epichlorohydrin at 20° C. over a period of 10 minutes. The reaction temperature increased to 28° C. The mixture was then heated at 65°-70° C. for 24 hours. The 1H NMR spectrum of the product was identical with that of Example 1. The material was used in the next step. The mixture was then heated at 65°-70° C. for 24 hours

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

Procedure: A solution of 30.5 g (0.20 mol) of 3-chloro-2-hydroxy-1-propyl acetate (prepared in Example 1), 22 g (0.30 mol) of ethyl vinyl ether, and 7.5 g (0.030 mol) of pyridinium p-toluenesulfonate in 150 mL of methylene chloride was stirred at room temperature for 6 hours. The solution was then washed with 75 mL of water, dried and stripped of solvent in vacuo to give 44.0 g (98.0%) of 3-chloro-2-(1-ethoxyethoxy)-1-propyl acetate: 1H NMR (CDCl3) δ1.05-1.37 (overlapping t and d, 6H, --CH2CH3 and --CHCH3); 2.07 (s, 3H, --COCH); 3.53 and 4.12 (m. 7H, --CH2CHCH2 and --CH2CH3); 4.72 (q, J=4 Hz, 1H, --CHCH3); IR (film) 1740 cm-1 (--COCH3 ). The unpurified product was used in the next step. The solution was then washed with 75 mL of water dried

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

Procedure: A solution of 271.9 g (1.78 moles) of 3-chloro-2-hydroxy-1-propyl acetate, 244 ml (2.67 moles) of freshly distilled dihydropyran, and 44.7 g (0.178 moles) of pyridinium p-toluenesulfonate in 1800 mL of methylene chloride was stirred at room temperature with cooling to control the reaction exotherm. After 22 hours the reaction mixture was washed with 500 mL of water and 250 mL of sodium chloride solution, and was dried over sodium sulfate. Solvent was removed and the residue was dried at 0.03 mm for 1.5 hours to give 473.3 g of crude 3-chloro-2-tetrahydropyranyloxy-1-propyl acetate: 1H NMR (CDCl3) δ1.63 (br. s, 6 H, (CH2)3); 2.08 (s, 3H, CH3CO); 3.5-4.3 (7H, CH2CHCH2); 4.73 (br. s, 1H, --O--CH); IR (neat, NaCl) 3000, 2910 (C--H); 1740 cm- 1 (--O--CO--CH3). with cooling the reaction exotherm After 22 hours the reaction mixture was washed with 500 mL of water and 250 mL of sodium chloride solution was dried over sodium sulfate Solvent was removed the residue was dried at 0.03 mm for 1.5 hours