乙基2-氰基-2-丙酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Prepared from ethyl 2-cyano-2-methylpropanoate (3 g, 21.25 mmol) according to the method described for 4-methyl-3-oxopentanenitrile in Example 122A Step 1, to afford 2,2-dimethyl-3-oxopentanedinitrile as a yellow oil (1.40 g, 48%) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.98 (s, 2H), 1.60 (s, 6H).

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

实验步骤: To a solution of ethyl 2-cyano-2-methylpropanoate (0.6 g, 4.2 mmol, 1.0 equiv) in 6 mL of ethanol/ammonium hydroxide (10:1) was added Ra/Ni (20%, 0.12 g). The resulting mixture was stirred under hydrogen at r.t. for 16 h. The catalyst was filtered off, and the filtrate was concentrated to give ethyl 3-amino-2,2-dimethylpropanoate (0.43 g, yield: 70%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 4.15 (q, 2H), 2.77 (s, 2H), 1.76 (s, 2H), 1.26 (t, 3H), 1.18 (s, 6H). The catalyst was filtered off the filtrate was concentrated

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

实验步骤: Prepared from ethyl 2-cyano-2-methylpropanoate (3 g, 21.25 mmol) according to the method described for 4-methyl-3-oxopentanenitrile in Example 122A Step 1, to afford 2,2-dimethyl-3-oxopentanedinitrile as a yellow oil (1.40 g, 48%) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.98 (s, 2H), 1.60 (s, 6H).

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

实验步骤: Prepared from ethyl 2-cyano-2-methylpropanoate (3 g, 21.25 mmol) according to the method described for 4-methyl-3-oxopentanenitrile in Example 122A Step 1, to afford 2,2-dimethyl-3-oxopentanedinitrile as a yellow oil (1.40 g, 48%) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.98 (s, 2H), 1.60 (s, 6H).

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

实验步骤: A mixture of diphenyldithiophosphonic acid (ALFAAESAR, 1.42 g, 5.67 mmol) and 2-cyano-2-methylpropionic acid ethyl ester (ABCR, 0.412 mL, 2.83 mmol) in isopropanol (30 mL) was heated under reflux for 4 h. Reaction mixture was cooled to room temperature and a precipitate was formed. Reaction flask was placed in the freezer for 1 h. Reaction mixture was filtered and filtrate was concentrated. Residue was taken up in DCM (100 mL) and washed with water (20 mL), 1N NaOH (20 mL), saturated NaHCO3 (20 mL) and dried over sodium sulfate and concentrated. The resulting oil was loaded on a 25 g silica cartridge and eluted with linear gradient 0-50% hexane-ethyl acetate to yield the title compound (110 mg, 0.628 mmol, 22.2% yield). Another impure batch was loaded on a 10 g silica cartridge and eluted with linear gradient 0-50% hexane-ethyl acetate to recover the title compound (120 mg, 0.685 mmol, 24.17% yield). Total yield: (230 mg, 1.313 mmol, 46.32%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.70 (br s, 1H), 8.86 (br s, 1H), 4.05 (q, 2H), 1.39 (s, 6H), 1.15 (t, 3H). [ES+MS] m/z 176 (MH+). was heated under reflux for 4 h Reaction mixture a precipitate was formed Reaction flask Reaction mixture was filtered filtrate was concentrated washed with water (20 mL), 1N NaOH (20 mL), saturated NaHCO3 (20 mL) dried over sodium sulfate concentrated eluted with linear gradient 0-50% hexane-ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: A mixture of diphenyldithiophosphonic acid (ALFAAESAR, 1.42 g, 5.67 mmol) and 2-cyano-2-methylpropionic acid ethyl ester (ABCR, 0.412 mL, 2.83 mmol) in isopropanol (30 mL) was heated under reflux for 4 h. Reaction mixture was cooled to room temperature and a precipitate was formed. Reaction flask was placed in the freezer for 1 h. Reaction mixture was filtered and filtrate was concentrated. Residue was taken up in DCM (100 mL) and washed with water (20 mL), 1N NaOH (20 mL), saturated NaHCO3 (20 mL) and dried over sodium sulfate and concentrated. The resulting oil was loaded on a 25 g silica cartridge and eluted with linear gradient 0-50% hexane-ethyl acetate to yield the title compound (110 mg, 0.628 mmol, 22.2% yield). Another impure batch was loaded on a 10 g silica cartridge and eluted with linear gradient 0-50% hexane-ethyl acetate to recover the title compound (120 mg, 0.685 mmol, 24.17% yield). Total yield: (230 mg, 1.313 mmol, 46.32%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.70 (br s, 1H), 8.86 (br s, 1H), 4.05 (q, 2H), 1.39 (s, 6H), 1.15 (t, 3H). [ES+MS] m/z 176 (MH+). was heated under reflux for 4 h Reaction mixture a precipitate was formed Reaction flask Reaction mixture was filtered filtrate was concentrated washed with water (20 mL), 1N NaOH (20 mL), saturated NaHCO3 (20 mL) dried over sodium sulfate concentrated eluted with linear gradient 0-50% hexane-ethyl acetate

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

实验步骤: To a solution of ethyl 2-cyano-2-methylpropanoate (0.6 g, 4.2 mmol, 1.0 equiv) in 6 mL of ethanol/ammonium hydroxide (10:1) was added Ra/Ni (20%, 0.12 g). The resulting mixture was stirred under hydrogen at r.t. for 16 h. The catalyst was filtered off, and the filtrate was concentrated to give ethyl 3-amino-2,2-dimethylpropanoate (0.43 g, yield: 70%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 4.15 (q, 2H), 2.77 (s, 2H), 1.76 (s, 2H), 1.26 (t, 3H), 1.18 (s, 6H). The catalyst was filtered off the filtrate was concentrated

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

实验步骤: A mixture of 73.5 g of 2-hydroxy-4,6-dimethoxyacetophenone, 260 g of dimethylcyanoacetic acid ethyl ester and 375 ml of absolute dioxane is introduced into a suspension of 28.6 g of NaH in 7.3 g of dimethylcyanoacetic acid ethyl ester at 0°-10°, while stirring. The mixture is heated for 1 hour at 80°, cooled and poured into acetic acid and the resulting solution is stirred into ice water to give 2,2-dimethyl-3,5-dioxo-5-(2-hydroxy-4,6-dimethoxyphenyl)-pentanonitrile; m.p. 112°-113°. The mixture is heated for 1 hour at 80° cooled

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

实验步骤: According to the procedure described in the synthesis method of Compound XIV-3 with the modification that the reaction was carried out for 3 days, ethyl 2-cyano-2-methylpropanoate (2.91 ml, 20 mmol) was hydrogenated with raney nickel (600 mg) to obtain the title compound (2.90 g, 100%). described in the synthesis method of Compound XIV-3 with the modification that the reaction

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

实验步骤: According to the procedure described in the synthesis method of Compound XIV-3 with the modification that the reaction was carried out for 3 days, ethyl 2-cyano-2-methylpropanoate (2.91 ml, 20 mmol) was hydrogenated with raney nickel (600 mg) to obtain the title compound (2.90 g, 100%). described in the synthesis method of Compound XIV-3 with the modification that the reaction