methyl 8-hydroxyoctanoate

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

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude methyl-8-hydroxy-octanoate (7, 1.24 g, 7.13 mmol, 1.0 equiv.) in CH2Cl2 (15 mL, 0.48M) at 0° C. was treated successively with CBr4 (3.07 g, 9.27 mmol, 1.3 equiv.) and PPh3 (2.61 g, 9.98 mmol, 1.4 equiv.) and the reaction mixture was stirred at 4° C. for 10 h. The, reaction mixture was then concentrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%): 1H NMR (CDCl3, 250 MHz) δ3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J =6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, CH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 6H, alkyl protons). The, reaction mixture was then concentrated under reduced pressure washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%)

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

Procedure: A solution of suberic acid monomethyl ester (15 g, 7.97 mmol, 1.0 equiv.) in tetrahydrofuran (THF) (32.0 mL, 0.25M) at -20° C. was treated ##STR1## dropwise with BH3.THF (1M solution in THF, 7.97 mL, 7.97 mmol, 1.0 equiv.). The reaction mixture was stirred overnight and was subsequently allowed to reach room temperature. The reaction mixture was then diluted with ethyl acetate (100 mL) and quenched with methanol (10 mL) and 10% HCl (10 mL). Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL), afforded methyl-8-hydroxy-octanoate (7) as a crude white solid. to reach room temperature quenched with methanol (10 mL) and 10% HCl (10 mL) Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL)

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cis-9,10-octadecenoamide, cis-11,12-octadecenoamide, and trans-9,10-octadecenoamide were prepared from their respective acids as follows: cis-9,10-octadecenoic acid (oleic acid) in CH2Cl2 (0.2M) at 0° C. was treated with oxalyl chloride (3 eq) and stirred at 25° for 4 hour. Removal of solvent followed by treatment with saturated aqueous NH4OH at 0° C. gave cis-9,10-octadecenoamide, which was purified by silica gel column chromatography (40-75% ethyl acetate-hexanes gradient elution). Cis-8,9-octadecenoamide was synthesized as follows: 1) Suberic acid monomethyl ester in THF at -20° C. was treated with BH3 -THF (1.05 eq) and stirred for 12 hour at 25° C. to afford methyl 8-hydroxyoctanoate (18); 2) Methyl 8-hydroxyoctanoate in CH2Cl2 at 0° C. was treated sequentially with CBr4 (1.3 eq) and Ph3P (1.4 eq) and stirred for 10 hour at 4° C. to give methyl 8-bromooctanoate; 3) Methyl 8-bromooctanoate was dissolved in CH3CN (0.8M) and warmed at reflux. Ph3P (1.1 eq) was added to the solution and stirring was continued for 20 hour to afford the corresponding phosphonium salt; 4) The phosphonium salt of methyl 8-bromooctanoate was dissolved in THF at 25° C. and treated with KHMDS (1.1 eq). After stirring at reflux for 1 hour, the solution was cooled to -78° C. and decanal (1.5 eq) was added. The mixture was allowed to warm to 25° C. and stirred for 30 minute to afford methyl cis-8,9-octadecenoate; 5) Methyl cis-8,9-octadecenoate was hydrolyzed to afford cis-8,9-octadecenoic acid with LiOH (3 eq) in THF-CH3OH--H2O (3:1:1); 6) Conversion of cis-8,9-octadecenoic acid to cis-8,9-octadecenoamide was conducted as described above.

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cis-9,10-octadecenoamide, cis-11,12-octadecenoamide, and trans-9,10-octadecenoamide were prepared from their respective acids as follows: cis-9,10-octadecenoic acid (oleic acid) in CH2Cl2 (0.2M) at 0° C. was treated with oxalyl chloride (3 eq) and stirred at 25° for 4 hour. Removal of solvent followed by treatment with saturated aqueous NH4OH at 0° C. gave cis-9,10-octadecenoamide, which was purified by silica gel column chromatography (40-75% ethyl acetate-hexanes gradient elution). Cis-8,9-octadecenoamide was synthesized as follows: 1) Suberic acid monomethyl ester in THF at -20° C. was treated with BH3 -THF (1.05 eq) and stirred for 12 hour at 25° C. to afford methyl 8-hydroxyoctanoate (18); 2) Methyl 8-hydroxyoctanoate in CH2Cl2 at 0° C. was treated sequentially with CBr4 (1.3 eq) and Ph3P (1.4 eq) and stirred for 10 hour at 4° C. to give methyl 8-bromooctanoate; 3) Methyl 8-bromooctanoate was dissolved in CH3CN (0.8M) and warmed at reflux. Ph3P (1.1 eq) was added to the solution and stirring was continued for 20 hour to afford the corresponding phosphonium salt; 4) The phosphonium salt of methyl 8-bromooctanoate was dissolved in THF at 25° C. and treated with KHMDS (1.1 eq). After stirring at reflux for 1 hour, the solution was cooled to -78° C. and decanal (1.5 eq) was added. The mixture was allowed to warm to 25° C. and stirred for 30 minute to afford methyl cis-8,9-octadecenoate; 5) Methyl cis-8,9-octadecenoate was hydrolyzed to afford cis-8,9-octadecenoic acid with LiOH (3 eq) in THF-CH3OH--H2O (3:1:1); 6) Conversion of cis-8,9-octadecenoic acid to cis-8,9-octadecenoamide was conducted as described above. was purified by silica gel column chromatography (40-75% ethyl acetate-hexanes gradient elution)

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude methyl-8-hydroxy-octanoate (7, 1.24 g, 7.13 mmol, 1.0 equiv.) in CH2Cl2 (15 mL, 0.48 M) at 0° C. was treated successively with CBr4 (3.07 g, 9.27 mmol, 1.3 equiv.) and PPh3 (2.61 g, 9.98 mmol, 1.4 equiv.) and the reaction mixture was stirred at 4° C. for 10 h. The reaction mixture was then concentrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2,5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%): 1H NMR (CDCl3,250 MHz) δ 3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J=6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, CH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 6H, alkyl protons). The reaction mixture was then concentrated under reduced pressure washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure Chromatography (SiO2,5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%)

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

Procedure: A solution of suberic acid monomethyl ester (1.5 g, 7.97 mmol, 1.0 equiv.) in tetrahydrofuran (THF) (32.0 mL, .25M) at −20° C. was treated dropwise with BH3.THF (IM solution in THF, 7.97 mL, 7.97 mmol, 1.0 equiv.). The reaction mixture was stirred overnight and was subsequently allowed to reach room temperature. The reaction mixture was then diluted with ethyl acetate (100 mL) and quenched with methanol (10 mL) and 10% HCl (10 mL). Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL), afforded methyl-8-hydroxy-octanoate to reach room temperature quenched with methanol (10 mL) and 10% HCl (10 mL) Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL)

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

Procedure: A solution of suberic acid monomethyl ester (1.5 g, 7.97 mmol, 1.0 equiv.) in tetrahydrofuran (THF) (32.0 mL, .25M) at −20° C. was treated dropwise with BH3.THF (IM solution in THF, 7.97 mL, 7.97 mmol, 1.0 equiv.). The reaction mixture was stirred overnight and was subsequently allowed to reach room temperature. The reaction mixture was then diluted with ethyl acetate (100 mL) and quenched with methanol (10 mL) and 10% HCl (10 mL). Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL), afforded methyl-8-hydroxy-octanoate to reach room temperature quenched with methanol (10 mL) and 10% HCl (10 mL) Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL)

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude methyl-8-hydroxy-octanoate (7, 1.24 g, 7.13 mmol, 1.0 equiv.) in CH2Cl2 (15 mL, 0.48 M) at 0° C. was treated successively with CBr4 (3.07 g, 9.27 mmol, 1.3 equiv.) and PPh3 (2.61 g, 9.98 mmol, 1.4 equiv.) and the reaction mixture was stirred at 4° C. for 10 h. The reaction mixture was then concentrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%): 1H NMR (CDCl3, 250 MHz) δ 3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J=6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, CH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 6H, alkyl protons). The reaction mixture was then concentrated under reduced pressure washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%)

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

Procedure: A solution of suberic acid monomethyl ester (1.5 g, 7.97 mmol, 1.0 equiv.) in tetrahydrofuran (THF) (32.0 mL, 0.25M) at −20° C. was treated dropwise with BH3.THF (1M solution in THF, 7.97 mL, 7.97 mmol, 1.0 equiv.). The reaction mixture was stirred overnight and was subsequently allowed to reach room temperature. The reaction mixture was then diluted with ethyl acetate (100 mL) and quenched with methanol (10 mL) and 10% HCl (10 mL). Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL), afforded methyl-8-hydroxy-octanoate (7) as a crude white solid. to reach room temperature quenched with methanol (10 mL) and 10% HCl (10 mL) Extraction with NaHCO3 (1×20 mL), water (2×10 mL), and brine (1×10 mL)

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

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude methyl-8-hydroxy-octanoate (7, 1.24 g, 7.13 mmol, 1.0 equiv.) in CH2Cl2 (15 mL, 0.48 M) at 0° C. was treated successively with CBr4 (3.07 g, 9.27 mmol, 1.3 equiv.) and PPh3 (2.61 g, 9.98 mmol, 1.4 equiv.) and the reaction mixture was stirred at 4° C. for 10 h. The reaction mixture was then concentrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%): 1H NMR (CDCl3, 250 MHz) δ 3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J=6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, CH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 6H, alkyl protons). The reaction mixture was then concentrated under reduced pressure washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 8 as a clear, colorless oil (1.25 g, 1.69 g theoretical, 74.0%)