5-chloropentan-1-ol

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:0.00; pressure:0.00; stir:

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

Procedure: A stirred solution of pentamethylene chlorohydrin (10.0 g, 0.0816 mol) in Et2O (165 ml) under nitrogen was treated with 3,4-dihydro-2H-pyran (10.3 g, 0.122 mol) and p-toluenesulfonic acid hydrate (0.5 g) and kept at ambient temperature for 4.5 hours. The mixture was washed with aqueous NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was distilled to give 4.06 g, bp 79°-82° C. (0.1-0.07 mm Hg) and 10.54 g, bp 82°-84° C. (0.1-0.07 mm Hg) of 5-chloropentyl 2-tetrahydropyranyl ether. The mixture was washed with aqueous NaHCO3 and brine dried (MgSO4) concentrated The residue was distilled

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

Procedure: 20.0 grams (0.1 mole) 2-octylmorpholine, 13 grams (0.1 mole) of 5-chloropentanol and 12 grams of triethylamine in 150 ml. toluene were kept at 140°-150° C. for 12 hours in an autoclave. After cooling, the organic phase was washed twice with water, dried, and the solvent was evaporated and the base distilled at 128° C./0.01 mm Hg.; yield: 22.0 grams (77%). After cooling the organic phase was washed twice with water dried the solvent was evaporated the base distilled at 128° C./0.01 mm Hg

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

Procedure: 5-chloro-1-pentanol (12.26 g, 0.1 mol) was dissolved in dry dichloromethane (400 mL). 3,4-Dihydro-2H-pyrane (12.62 g, 0.15 mol) and pyridine toluene-4-sulphonate (1.26 g, 5 mmol) was then added and the reaction mixture was stirred magnetically in a nitrogen atmosphere at room temperature over night. Sodium-hydrogen-carbonate, saturated solution (150 mL) was added and the phases were separated. The aqueous phase was then extracted with dichloromethane (4×25 mL). The combined dichloromethane phases were washed with water (2×20 mL) and then dried (MgSO4). Dichloromethane was then distilled out on a rotary evaporator and yielded 19.6 g (95%) of a pale yellow oil. NMR indicated a pure product. the phases were separated The aqueous phase was then extracted with dichloromethane (4×25 mL) The combined dichloromethane phases were washed with water (2×20 mL) dried (MgSO4) Dichloromethane was then distilled out on a rotary evaporator

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

Procedure: 5-chloro-1-pentanol (12.26 g, 0.1 mol) was dissolved in dry dichloromethane (400 mL). 3,4-Dihydro-2H-pyrane (12.62 g, 0.15 mol) and pyridine toluene-4-sulphonate (1.26 g, 5 mmol) was then added and the reaction mixture was stirred magnetically in a nitrogen atmosphere at room temperature over night. Sodium-hydrogen-carbonate, saturated solution (150 mL) was added and the phases were separated. The aqueous phase was then extracted with dichloromethane (4×25 mL). The combined dichloromethane phases were washed with water (2×20 mL) and then dried (MgSO4). Dichloromethane was then distilled out on a rotary evaporator and yielded 19.6 g (95%) of a pale yellow oil. NMR indicated a pure product. the phases were separated The aqueous phase was then extracted with dichloromethane (4×25 mL) The combined dichloromethane phases were washed with water (2×20 mL) dried (MgSO4) Dichloromethane was then distilled out on a rotary evaporator

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))

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

Procedure: 1-(5-Hydroxypentyl)-4-piperidone is prepared from 4-piperidone and 1-chloro-5-hydroxypentane essentially as described above in Example 38, Scheme C, step a.