2-[2-(hydroxymethyl)piperidin-1-yl]acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S6 using 2-hydroxymethyl-piperidin-1-yl-acetonitrile (31.96 g, 0.208 mol), LiAlH4 (23.68 g, 0.624 mol) and dry THF (200 mL). The title compound (8.74 g, 27%) was afforded as straw-coloured oil by kugelrohr distillation (225° C., 0.13 mbar). δH (250 MHz; CDCl3); 1.2-1.75 (m, 6H, CH2CH2CH2, CH2CH2CH and CH2CH2CH), 2.2 (m, 1H, 1×NCH2CH2) 2.35 (m, 2H, H2NCH2CH2N), 2.58 (s (broad), 3H, OH and NH2), 2.75 (t, 2H, H2NCH2CH2N), 2.85 (3×d, 1H, 1×NCH2CH2), 2.92 (m, 1H, NCHCH2), 3.4 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH) and 3.76 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH; FAB MS, m/z(M+H)+ 159.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S3 using 2-piperidinemethanol (26.50 g, 0.230 mol), BrCH2CN (30.35 g, 0.253 mol), Et3N (35.27 mL, 0.253 mol) and dry THF (150 mL). The crude product was purified by flash chromatography using ether/CH3OH (19:1) as eluent. The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%). δH(250 MHz; CDCl3); 1.2-1.85 (m, 6H, NCH2CH2CH2, CH2CH2CH2CH and CH2CH2CH), 2.05 (s (broad), 6H, OH), 2.4 (m, 1H, NCH2CH2), 2.55 (3×d, 1H. 1×NCH2CH2), 2.95 (m, 1H, NCHCH2), 3.45 (d, 1H, J=17 Hz, 1×NCH2CN), 3.5 (2×d, 1H, J=3 Hz and 12 Hz, 1×CHCH2OH), 3.76 (2×d, 1H, J=3 Hz and 12 Hz, CHCH2OH) and 4.05 (d, 1H, J=17 Hz, 1×NCH2CN); δC (62.9 MHz; CDCl3); 23.71, 25.25, 28.69, 43.43, 54.04, 60.73, 64.46 and 115.05 (CN); FAB MS, m/z(M+H)+ 155; IR υmax/cm−1; 3400 (OH, m broad), 2350 and 2240 (CN) and 1650. The crude product was purified by flash chromatography The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S6 using 2-hydroxymethyl-piperidin-1-yl-acetonitrile (31.96 g, 0.208 mol), LiAlH4 (23.68 g, 0.624 mol) and dry THF (200 mL). The title compound (8.74 g, 27%) was afforded as straw-coloured oil by kugelrohr distillation (225° C., 0.13 mbar). δH (250 MHz; CDCl3); 1.2-1.75 (m, 6H, CH2CH2CH2, CH2CH2CH and CH2CH2CH), 2.2 (m, 1H, 1×NCH2CH2) 2.35 (m, 2H, H2NCH2CH2N), 2.58 (s (broad), 3H, OH and NH2), 2.75 (t, 2H, H2NCH2CH2N), 2.85 (3×d, 1H, 1×NCH2CH2), 2.92 (m, 1H, NCHCH2), 3.4 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH) and 3.76 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH; FAB MS, m/z(M+H)+ 159.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S3 using 2-piperidinemethanol (26.50 g, 0.230 mol), BrCH2CN (30.35 g, 0.253 mol), Et3N (35.27 mL, 0.253 mol) and dry THF (150 mL). The crude product was purified by flash chromatography using ether/CH3OH (19:1) as eluent. The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%). δH(250 MHz; CDCl3); 1.2-1.85 (m, 6H, NCH2CH2CH2, CH2CH2CH2CH and CH2CH2CH), 2.05 (s (broad), 6H, OH), 2.4 (m, 1H, NCH2CH2), 2.55 (3×d, 1H. 1×NCH2CH2), 2.95 (m, 1H, NCHCH2), 3.45 (d, 1H, J=17 Hz, 1×NCH2CN), 3.5 (2×d, 1H, J=3 Hz and 12 Hz, 1×CHCH2OH), 3.76 (2×d, 1H, J=3 Hz and 12 Hz, CHCH2OH) and 4.05 (d, 1H, J=17 Hz, 1×NCH2CN); δC (62.9 MHz; CDCl3); 23.71, 25.25, 28.69, 43.43, 54.04, 60.73, 64.46 and 115.05 (CN); FAB MS, m/z(M+H)+ 155; IR υmax/cm−1; 3400 (OH, m broad), 2350 and 2240 (CN) and 1650. The crude product was purified by flash chromatography The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S6 using 2-hydroxymethyl-piperidin-1-yl-acetonitrile (31.96 g, 0.208 mol), LiAlH4 (23.68 g, 0.624 mol) and dry THF (200 mL). The title compound (8.74 g, 27%) was afforded as straw-coloured oil by kugelrohr distillation (225° C., 0.13 mbar). δH (250 MHz; CDCl3); 1.2-1.75 (m, 6H, CH2CH2CH2, CH2CH2CH and CH2CH2CH), 2.2 (m, 1H, 1×NCH2CH2) 2.35 (m, 2H, H2NCH2CH2N), 2.58 (s (broad), 3H, OH and NH2), 2.75 (t, 2H, H2NCH2CH2N), 2.85 (3×d, 1H, 1×NCH2CH2), 2.92 (m, 1H, NCHCH2), 3.4 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH) and 3.76 (2×d, 1H, J=4 Hz and 12 Hz, 1×CHCH2OH; FAB MS, m/z(M+H)+ 159.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method follows that of S3 using 2-piperidinemethanol (26.50 g, 0.230 mol), BrCH2CN (30.35 g, 0.253 mol), Et3N (35.27 mL, 0.253 mol) and dry THF (150 mL). The crude product was purified by flash chromatography using ether/CH3OH (19:1) as eluent. The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%). δH(250 MHz; CDCl3); 1.2-1.85 (m, 6H, NCH2CH2CH2, CH2CH2CH2CH and CH2CH2CH), 2.05 (s (broad), 6H, OH), 2.4 (m, 1H, NCH2CH2), 2.55 (3×d, 1H. 1×NCH2CH2), 2.95 (m, 1H, NCHCH2), 3.45 (d, 1H, J=17 Hz, 1×NCH2CN), 3.5 (2×d, 1H, J=3 Hz and 12 Hz, 1×CHCH2OH), 3.76 (2×d, 1H, J=3 Hz and 12 Hz, CHCH2OH) and 4.05 (d, 1H, J=17 Hz, 1×NCH2CN); δC (62.9 MHz; CDCl3); 23.71, 25.25, 28.69, 43.43, 54.04, 60.73, 64.46 and 115.05 (CN); FAB MS, m/z(M+H)+ 155; IR υmax/cm−1; 3400 (OH, m broad), 2350 and 2240 (CN) and 1650. The crude product was purified by flash chromatography The title-compound was crystallised from ether yielding cream-coloured crystals (31.46 g, 89%)