1-chloro-3-phenoxypropan-2-ol

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

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8N Jones reagent (100 ml.) was added dropwise to a stirred solution of 1-chloro-2-hydroxy-3-phenoxypropane (28.3 g.) in acetone (100 ml.) during 1 hour while maintaining the reaction temperature at 20° C. The mixture was then stirred for 4 hours, and then sufficient water was added to dissolve the precipitated chromium salts. The mixture was extracted three times with diethyl ether and the combined ethereal extracts were dried over sodium sulphate, concentrated under reduced pressure, dried again over sodium sulphate, and concentrated further and distilled, to give 1-chloro-3-phenoxyacetone (13.9 g.), b.p. 150°-155° C./20 mm.Hg. The mixture was extracted three times with diethyl ether the combined ethereal extracts were dried over sodium sulphate concentrated under reduced pressure dried again over sodium sulphate concentrated further distilled

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

Procedure: A mixture of 75 g of 7-(3-aminopropyl)-theophylline and 27.4 g of 1-chloro-3-phenoxy-2-propanol is heated for 8 hours at 130° to 140° C. After the melt has been cooled to 70°-90° C., ethanol is added to it, followed by brief boiling under reflux. After standing overnight, the untreated and precipitated aminopropyl theophylline hydrochloride is filtered off under suction, the filtrate is acidified with alcoholic hydrochloric acid, heavily concentrated and acetone added until crystallisation begins. The reaction product then separates and is recrystallised from methanol. Yield 30.2 g. Melting point of the hydrochloride: 183°-186° C. is heated for 8 hours at 130° to 140° C After the melt has been cooled to 70°-90° C. under reflux the untreated and precipitated aminopropyl theophylline hydrochloride is filtered off under suction heavily concentrated acetone added until crystallisation is recrystallised from methanol 183°-186° C.

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

Procedure: A solution of 9.3 g. (0.05 mole) of 1-chloro-2-hydroxy-3-phenoxypropane in 100 ml. of tetrahydrofuran is mixed with a solution of 8.1 g. (0.05 mole) of trichloroacetamidine, also in tetrahydrofuran. The mixture is heated at reflux for 3 hours, and concentrated to an oil, which is taken up in benzene and washed well with water. The benzene layer is dried over magnesium sulfate, filtered, and treated with excess ethanolic hydrogen chloride to provide the crude hydroxy amidine hydrochloride. This is dissolved in glacial acetic acid and converted to the acetate by treatment with 3.5 g. (0.04 mole) of acetyl chloride at room temperature for 3 days. The reaction mixture is evaporated, treated with benzene, evaporated to dryness, and the process repeated once more with benzene, twice with toluene and twice with petroleum ether. There is afforded N-(2-acetoxy-3-phenoxypropyl) trichloroacetamidine hydrochloride, m.p. 70° to 77° C. The mixture is heated at reflux for 3 hours concentrated to an oil, which washed well with water The benzene layer is dried over magnesium sulfate filtered treated with excess ethanolic hydrogen chloride to provide the crude hydroxy amidine hydrochloride The reaction mixture is evaporated treated with benzene evaporated to dryness

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

Procedure: A solution of 9.3 g. (0.05 mole) of 1-chloro-2-hydroxy-3-phenoxypropane in 100 ml. of tetrahydrofuran is mixed with a solution of 8.1 g. (0.05 mole) of trichloroacetamidine, also in tetrahydrofuran. The mixture is heated at reflux for 3 hours, and concentrated to an oil, which is taken up in benzene and washed well with water. The benzene layer is dried over magnesium sulfate, filtered, and treated with excess ethanolic hydrogen chloride to provide the crude hydroxy amidine hydrochloride. This is dissolved in glacial acetic acid and converted to the acetate by treatment with 3.5 g. (0.04 mole) of acetyl chloride at room temperature for 3 days. The reaction mixture is evaporated, treated with benzene, evaporated to dryness, and the process repeated once more with benzene, twice with toluene and twice with petroleum ether. There is afforded N-(2-acetoxy-3-phenoxypropyl) trichloroacetamidine hydrochloride, m.p. 70° to 77° C. The mixture is heated at reflux for 3 hours concentrated to an oil, which washed well with water The benzene layer is dried over magnesium sulfate filtered treated with excess ethanolic hydrogen chloride to provide the crude hydroxy amidine hydrochloride The reaction mixture is evaporated treated with benzene evaporated to dryness

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8N Jones reagent (100 ml.) was added dropwise to a stirred solution of 1-chloro-2-hydroxy-3-phenoxypropane (28.3 g.) in acetone (100 ml.) during 1 hour while maintaining the reaction temperature at 20° C. The mixture was then stirred for 4 hours, and then sufficient water was added to dissolve the precipitated chromium salts. The mixture was extracted three times with diethyl ether and the combined ethereal extracts were dried over sodium sulphate, concentrated under reduced pressure, dried again over sodium sulphate, and concentrated further and distilled, to give 1-chloro-3-phenoxyacetone (13.9 g.), b.p. 150°-155° C./20 mm.Hg. The mixture was extracted three times with diethyl ether the combined ethereal extracts were dried over sodium sulphate concentrated under reduced pressure dried again over sodium sulphate concentrated further distilled

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

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8 N Jones reagent (100 ml.) was added dropwise to a stirred solution of 1-chloro-2-hydroxy-3-phenoxypropane (28.3 g.) in acetone (100 ml.) during 1 hour while maintaining the reaction temperature at 20° C. The mixture was then stirred for 4 hours, and then sufficient water was added to dissolve the precipitated chromium salts. The mixture was extracted three times with diethyl ether and the combined ethereal extracts were dried over sodium sulphate, concentrated under reduced pressure, dried again over sodium sulphate, and concentrated further and distilled, to give 1-chloro-3-phenoxyacetone (13.9 g.), b.p. 150°-155° C./20 mm.Hg. The mixture was extracted three times with diethyl ether the combined ethereal extracts were dried over sodium sulphate concentrated under reduced pressure dried again over sodium sulphate concentrated further distilled

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

Procedure: To a warm stirred suspension of 3,4-dihydro-7-hydroxy-4-iminocoumarin (17.7g; 0.1 mole) in dry DMF (75 ml) was added sodium hydride (2.4; 0.1 mole) portionwise and the mixture refluxed for 1.5 hours to complete formation of the sodium salt. A solution of 1-chloro-3-phenoxy-2-propanol (18.7 g; 0.1 mole) of dry DMF (10 ml) was added dropwise at reflux and the mixture stirred at reflux for an additional 4 hours. The solvent was removed in vacuo and water (200 ml) added to the residue. The yellow solid was filtered off, washed well with water and dried in vacuo over P2O5 to give 30.0g (92%) of crude product which was suitable for most purposes. Recrystallisation from ethyl acetate gave material of m.p. 213°-214°; νmax (mull) 3320, 3200, complex carbonyl region 1690-1590cm-1,. τ(DSMO); 5.82(5H, m); 5.35(2H, broad exchangeable s); 4.85(1H, s); 3.20-2.52(8H, m with 1 proton removed after D2O exchange); 2.02(1H, d,) (Found; C, 64.52; H, 5.26; N, 3.78; C18H17NO5 0.5H2O requires; C, 64.28; H, 5.39; N, 4.16%). the mixture refluxed for 1.5 hours at reflux the mixture stirred at reflux for an additional 4 hours The solvent was removed in vacuo and water (200 ml) added to the residue The yellow solid was filtered off washed well with water dried in vacuo over P2O5

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

Procedure: A mixture of phenol (94g; 1.0 mole) and epichlorhydrin (138.8g; 1.5 mole) was vigorously stirred at 100° C. in the presence of piperidine hydrochloride (2.0g) for 6 hours, cooled, and the excess epichlorhydrin removed at 100° in vacuo. The residue was cooled, dissolved in an equal volume of chloroform and stirred vigorously with excess concentrated hydrochloric acid for 0.5 hours. After separatiin of the phases the organic layer was washed with water, dried and evaporated to a colourless oil. Distillation gave 116.4g (62.5%) of 1-chloro-3-phenoxy-2-propanol of bp0.6 112° as a GLC pure material, νmax (film) 3310, 1603, 1590, 1495, 1245cm-1 ; τ(CDCl3); 7.40 (broad exchangeable s); 6.25 (2H, d, J 3.5Hz); 5.90 (2H, s); 5.90 (1H, m); 3.21-2.56 (5H,m). cooled the excess epichlorhydrin removed at 100° in vacuo The residue was cooled dissolved in an equal volume of chloroform After separatiin of the phases the organic layer was washed with water dried evaporated to a colourless oil Distillation

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

Procedure: A mixture of 55 g (0.29 mol) of 1-chloro-2-hydroxy-3-phenoxypropane, 170 g (1.1 mol) sodium iodide in 1.0 of acetone is refluxed in the dark under a nitrogen atmosphere for 3 days. The acetone is removed in vacuo, the residue slurried in chloroform, filtered and the filtrate stripped to afford the title compound. is refluxed in the dark under a nitrogen atmosphere for 3 days The acetone is removed in vacuo filtered

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

Procedure: To a warm stirred suspension of 3,4-dihydro-7-hydroxy-4-iminocoumarin (17.7 g; 0.1 mole) in dry DMF (75 ml) was added sodium hydride (2.4; 0.1 mole) portionwise and the mixture refluxed for 1.5 hours to complete formation of the sodium salt. A solution of 1-chloro-3-phenoxy-2-propanol (18.7 g; 0.1 mole) in dry DMF (10 ml) was added dropwise at reflux and the mixture stirred at reflux for an additional 4 hours. The solvent was removed in vacuo and water (200 ml) added to the residue. The yellow solid was filtered off, washed well with water and dried in vacuo over P2O5 to give 30.0 g (92%) of crude product which was suitable for most purposes. Recrystallisation from ethyl acetate gave material of m.p. 213°-214°; νmax (mull) 3320, 3200, complex carbonyl region 1690-1590 cm-1, τ(DSMO); 5.82(5H, m); 5.35(2H, broad exchangeable s); 4.85(1H, s); 3.20-2.52(8H, m with 1 proton removed after D2O exchange); 2.02(1H, d,) (Found; C, 64.52; H, 5.26; N, 3.78; C18H17NO5 0.5H2O requires; C, 64.28; H, 5.39; N, 4.16%). the mixture refluxed for 1.5 hours at reflux the mixture stirred at reflux for an additional 4 hours The solvent was removed in vacuo and water (200 ml) added to the residue The yellow solid was filtered off washed well with water dried in vacuo over P2O5