1-nitrohexane

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

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

Procedure: The resulting nitrohexanol acetate of formula 9 is then reduced using a boron-based reducing agent, e.g., sodium borohydride, in a 2° or 3° alkanol at 25°-80° C. for 3-15 hours to produce a nitrohexane derivative of formula 10 (step 8). For example, O-acetyl-1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexan-3-ol (9) is heated with NaBH4 in 2-propanol at reflux for 3-15 hours to yield 1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(prop-2-yl)-6-(3,4-dimethoxyphenyl)hexane (10).

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

Procedure: 6-Phenylhexanoic acid (0.150 g, 0.78 mmol) and CDI (0.253 g, 1.56 mmol) were added together and then reacted with nitrohexane (0.153 g, 1.17 mmol) and DBU (0.297 g, 1.95 mmol) according to the general procedure. Purification by column chromatography gave 0.090 g (38%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.28 (m, 2H), 7.17 (m, 3H), 5.11 (dd, J=4.8, 10.4 Hz, 1H), 2.61 (m, 4H), 1.63 (m, 6H), 1.33 (m, 8H) 0.90 (t, J=6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 199.5, 142.5, 128.6, 128.5, 126.0, 94.6, 39.5, 35.9, 31.3, 31.2, 29.9, 28.7, 25.7, 23.3, 22.4, 14.1 ppm; IR νmax (cm−1) 3027, 2930, 2858, 1731, 1559, 1454, 1363, 1030, 748, 699; HRMS (FAB) calcd for C18H27NO3 (MNa+) 328.1883, found 328.1881. Purification by column chromatography gave 0.090 g (38%) as a yellow oil

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

Procedure: The product was obtained analogously to IP 5d starting from 1.23 g (5.57 mmol) of (3R,4S)-1-benzyl-4-methylpiperidin-3,4-diol. Yield: 730 mg (quant. yield); C6H13NO2 (M=131.173); calc.: molpeak (M+H)+: 132; found: molpeak (M+H)+: 132; HPLC-MS: 0.93 minutes (method C). 0.93 minutes (method C)

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

Procedure: The resulting nitrohexanol acetate of formula 9 is then reduced using a boron-based reducing agent, e.g., sodium borohydride, in a 2° or 3° alkanol at 25°-80° C. for 3-15 hours to produce a nitrohexane derivative of formula 10 (step 8). For example, O-acetyl-1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexan-3-ol (9) is heated with NaBH4 in 2-propanol at reflux for 3-15 hours to yield 1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(prop-2-yl)-6-(3,4-dimethoxyphenyl)hexane (10).

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

Procedure: The resulting nitrohexanol acetate of formula 9 is then reduced using a boron-based reducing agent, e.g., sodium borohydride, in a 2° or 3° alkanol at 25°-80° C. for 3-15 hours to produce a nitrohexane derivative of formula 10 (step 8). For example, O-acetyl-1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexan-3-ol (9) is heated with NaBH4 in 2-propanol at reflux for 3-15 hours to yield 1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(prop-2-yl)-6-(3,4-dimethoxyphenyl)hexane (10).

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

Procedure: A suspension of ethyl acrylate, 1-nitrohexane, K2CO3, and Aliquat 336 (6 drops) is sonicated for 5 h. To the reaction is added Et2O. The reaction mixture is filtered, extracted with brine, dried over Na2SO4 (anhydrous), filtered, and concentrated under reduced pressure to give a yellow liquid. The product is purified by column chromatography to give methyl 4-nitrononanoate. is sonicated for 5 h The reaction mixture is filtered extracted with brine dried over Na2SO4 (anhydrous) filtered concentrated under reduced pressure to give a yellow liquid The product is purified by column chromatography

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

Procedure: A suspension of ethyl acrylate, 1-nitrohexane, K2CO3, and Aliquat 336 (6 drops) is sonicated for 5 h. To the reaction is added Et2O. The reaction mixture is filtered, extracted with brine, dried over Na2SO4 (anhydrous), filtered, and concentrated under reduced pressure to give a yellow liquid. The product is purified by column chromatography to give methyl 4-nitrononanoate. is sonicated for 5 h The reaction mixture is filtered extracted with brine dried over Na2SO4 (anhydrous) filtered concentrated under reduced pressure to give a yellow liquid The product is purified by column chromatography

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

Procedure: A suspension of ethyl acrylate, 1-nitrohexane, K2CO3, and Aliquat 336 (6 drops) is sonicated for 5 h. To the reaction is added Et2O. The reaction mixture is filtered, extracted with brine, dried over Na2SO4 (anhydrous), filtered, and concentrated under reduced pressure to give a yellow liquid. The product is purified by column chromatography to give methyl 4-nitrononanoate. is sonicated for 5 h The reaction mixture is filtered extracted with brine dried over Na2SO4 (anhydrous) filtered concentrated under reduced pressure to give a yellow liquid The product is purified by column chromatography

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

Procedure: The resulting nitrohexanol acetate of formula 9 is then reduced using a boron-based reducing agent, e.g., sodium borohydride, in a 2° or 3° alkanol at 25°-80° C. for 3-15 hours to produce a nitrohexane derivative of formula 10 (step 8). For example, O-acetyl-1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexan-3-ol (9) is heated with NaBH4 in 2-propanol at reflux for 3-15 hours to yield 1-(3,4-dimethoxyphenyl)-2-nitro-6-cyano-6-(prop-2-yl)-6-(3,4-dimethoxyphenyl)hexane (10).

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

Procedure: n-BuLi (1.6 M in hexane, 6.24 mL) was added dropwise with stirring to a solution of nitrohexane (1.4 mL, 10 mmol) in THF (12 mL) at -78° C. After 15 minutes a solution of TiCl3 (OPriso) (5 mmol) in THF (2 mL) and CH2Cl2 (3 mL) solution was added. After a further 15 minutes 4-nitrobenzaldehyde (0.75 mL, 5 mmol) in CH2Cl2 (3 mL) was added and the mixture allowed to warm up to room temperature (18 30 min.). Stirring was continued for a further 3.5 hours at room temperature and the mixture was quenched with an aqueous slurry of disodium EDTA (1.86 g, 5 mmol) and extracted with Et2O (3×75 mL), aqueous sodium bicarbonate (75 mL) and water (75 mL), dried and evaporated in vacuo. Flash column chromatography [SiO2, hexane:Et2O, 4:1 v/v] gave 1-(4-nitrophenyl)2 -nitro-heptan-1-ol (1.13 g, 81% Erythro:threo ratio 3.9:1 extracted with Et2O (3×75 mL), aqueous sodium bicarbonate (75 mL) and water (75 mL) dried evaporated in vacuo

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

Procedure: Following a procedure similar to that described in Preparation 9, except that equivalent amounts of 2-chlorobenzaldehyde and nitrohexane were used in place of the 2-fluorobenzaldehyde and nitropropane, the title compound was obtained as a pale yellow oil in a yield of 17%.