43% |
Stage #1: 3-hydroxymethylpyridin; Trimethylacetic acid With ammonium peroxydisulfate; sulfuric acid; silver nitrate In water at 20℃; for 2h;
Stage #2: With ammonium hydroxide In water |
18
3-Pyridinemethanol (2.2 g, 20.2 mmol), pivalic acid (10.3 g, 100.8 mmol) and silver nitrate (0.68, 4.0 mmol) were suspended in 10% aqueous H2SO4 (20 ml). Ammonium persulfate (9.2 g, 40.3 mmol) in H2O (40 ml) was added to the mixture. The mixture was stirred at r.t. for 2.0 h. NH4OH was added until pH=9. The product was extracted with EtOAc. The combined organic extracts were washed with water, dried (MgSO4), filtered and concentrated. Purification was done by flash chromatography (Pet. Ether/EtOAc 70:30) to give the title substance in 43% yield.1H NMR (CDCl3) δ 10.08 (s, IH), 9.01 (bs, IH), 8.10 (m, IH), 7.51 (d, J=8.4 Hz, IH), 1.40 (s, 9H). |
43% |
Stage #1: 3-hydroxymethylpyridin; Trimethylacetic acid With ammonium peroxydisulfate; sulfuric acid; silver nitrate In water at 20℃; for 2h;
Stage #2: With ammonium hydroxide In water |
85
6-tert-Butylnicotinaldehyde 3-Pyridinemethanol (2.2 g, 20.2 mmol), pivalic acid (10.3 g, 100.8 mmol) and silver nitrate (0.68, 4.0 mmol) were suspended in 10% aqueous H2SO4 (20 ml). Ammonium persulfate (9.2 g, 40.3 mmol) in H2O (40 ml) was added to the mixture. The mixture was stirred at r.t. for 2.0 h. NH4OH was added until pH=9. The product was extracted with EtOAc. The combined organic extracts were washed with water, dried (MgSO4), filtered and concentrated. Purification was done by flash chromatography (Pet. Ether/EtOAc 70:30) to give the title substance in 43% yield. 1H NMR (CDCl3) δ 10.08 (s, 1H), 9.01 (bs, 1H), 8.10 (m, 1H), 7.51 (d, J=8.4 Hz, 1H), 1.40 (s, 9H). |
35% |
With ammonium persulfate; sulfuric acid; silver nitrate In water at 20℃; for 2h; |
1.1 Step-1 : [00159] Preparation of 6-(tert-butyl)nicotinaldehyde 2:
To a stirred solution of pyridin-3-yl-methanol (1 , 0.5 g, 4.58 mmol), pivalic acid (2.34 g, 22.9 mmol) and silver nitrate (0.155 g, 0.91 mmol) in 10% aqueous sulfuric acid solution (4.5 mL) was added a solution of ammonium persulfate (2.09 g, 9.16 mmol) in water (10 mL). The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was basified to pH 9 with aqueous ammonia and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. The crude product was purified by silica gel column chromatography using 20% ethyl acetate in hexane to afford the title compound 6-(tert-butyl)nicotinaldehyde (2, 0.26 g, 35%) as a pale yellow liquid. Calculated (M+H): 164.1 ; Found (M+H): 164.1 |