甲基 1-(氰甲基)环己烷-1-羧酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0° C. mixture of 1-cyanomethyl-cyclohexanecarboxylic acid methyl ester (4.28 g, 23.6 mmol) and cobalt (II) chloride hexahydrate (2.81 g, 11.8 mmol) in THF (80 mL) and water (40 mL) is treated portion-wise with sodium borohydride (4.47 g, 0.118 mol) and is warmed to room temperature and stirred for 48 hours under N2. The reaction is treated with 28% ammonium hydroxide (3.1 mL) and filtered through hyflo. The solvent is removed from the filtrate in vacuo and the residue is diluted with minimal water and brine and is extracted three times with 3:1 chloroform:isopropanol. The organic layer is dried (Na2SO4) and the solvent is removed in vacuo to afford crude product that is purified with a 0 to 10% methanol in CH2Cl2 gradient on silica gel to afford 1.95 g (54%) of the titled product. Rf=0.46 (9/1 CH2Cl2/methanol). MS (m/z): 154 (M+). filtered through hyflo The solvent is removed from the filtrate in vacuo the residue is diluted with minimal water and brine is extracted three times with 3:1 chloroform The organic layer is dried (Na2SO4) the solvent is removed in vacuo to afford crude product that is purified with a 0 to 10% methanol in CH2Cl2 gradient on silica gel

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Treat a −78° C. solution of methyl cyclohexane carboxylate (15.0 g, 0.105 mol) in THF (150 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (63.3 mL, 0.126 mol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (25.31 g, 0.211 mol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Acidify the reaction with 1 N HCl and then dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product. Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel to afford 7.78 g (41%) of the titled product. Rf=0.32 (3/1 hexanes/ethyl acetate). Treat stir at −78° C. for 15 minutes Warm the reaction to room temperature stir 4 hours dilute wash with water Dry the organic layer (Na2SO4) remove the solvent in vacuo to afford crude product Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Treat a −78° C. solution of methyl cyclohexane carboxylate (15.0 g, 0.105 mol) in THF (150 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (63.3 mL, 0.126 mol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (25.31 g, 0.211 mol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Acidify the reaction with 1 N HCl and then dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product. Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel to afford 7.78 g (41%) of the titled product. Rf=0.32 (3/1 hexanes/ethyl acetate). Treat stir at −78° C. for 15 minutes Warm the reaction to room temperature stir 4 hours dilute wash with water Dry the organic layer (Na2SO4) remove the solvent in vacuo to afford crude product Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Treat a −78° C. solution of methyl cyclohexane carboxylate (15.0 g, 0.105 mol) in THF (150 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (63.3 mL, 0.126 mol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (25.31 g, 0.211 mol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Acidify the reaction with 1 N HCl and then dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product. Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel to afford 7.78 g (41%) of the titled product. Rf=0.32 (3/1 hexanes/ethyl acetate). Treat stir at −78° C. for 15 minutes Warm the reaction to room temperature stir 4 hours dilute wash with water Dry the organic layer (Na2SO4) remove the solvent in vacuo to afford crude product Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel