Morpholine → 4-[(6-Methylpyridin-3-yl)methyl]morpholine

HRID 423142ノート

反応式

HRID 423142 の反応式
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:7][C:8]1[N:13]=[CH:12][C:11]([CH2:14]OS(C)(=O)=O)=[CH:10][CH:9]=1>O1CCCC1>[CH3:7][C:8]1[N:13]=[CH:12][C:11]([CH2:14][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:10][CH:9]=1

参加物

4

反応物 2

HCID 8083MorpholineHCID 58278804Methanesulfonic acid 6-methyl-pyridin-3-ylmethyl ester

生成物 1

HCID 207917014-[(6-Methylpyridin-3-yl)methyl]morpholine収率 67%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
20 °C

実験手順

Morpholine (43.2 kg, 495.9 mol) was then added over 2 hrs to the solution of methanesulfonic acid 6-methyl-pyridin-3-ylmethyl ester (198 mol; Example 1) in tetrahydrofuran (161 kg) under nitrogen at 15-20° C. and the resulting slurry stirred for 19 hrs. The suspension was filtered through a Silica (15.5 kg) column and the cake washed five times with tetrahydrofuran (43.5 kg). 440 L of the solution was then removed under vacuum distillation and heptane (41.52 kg) added. This was repeated two more times followed by the addition of heptane (48.6 kg) and the solution filtered through a Celite® (4.08 kg) bed at 40° C. and the cake washed twice with heptane (7.2 kg). Then the filtrate cooled to 20° C. over 3 hrs then to −12° C. over 5 hrs and held for 12 hrs at −12° C. The suspension was filtered and the cake washed with cold (0° C.) heptane (8.5 kg) and then dryed at 25° C. under vacuum, which gave 25.44 kg, 67% yield of 4-(6-Methyl-pyridin-3-ylmethyl)-morpholine as a beige solid. 1H NMR (400 MHz; CDCl3): δ 8.4 (d, J=1.72 Hz, 1H), 7.54 (dd, J=2.1, 7.91 Hz, 1H), 7.1 (d, J=7.92 Hz, 1H), 3.68 (apparent t, J=4.6, 9.28 Hz, 4H), 3.4 (s, 2H), 2.5 (s, 3H), 2.4 (apparent t, J=4.5, 8.93 Hz, 4H); 13C NMR (100 MHz, CDCl3): δ 157.3, 149.8, 137.2, 129.9, 122.9, 66.9, 60.3, 53.5, 24.1 ppm; MS (ESI) m/z 193 [M+1]+; Melting point: 51-52° C.

後処理

  1. filtrationThe suspension was filtered through a Silica (15.5 kg) column
  2. washthe cake washed five times with tetrahydrofuran (43.5 kg)
  3. custom440 L of the solution was then removed under vacuum distillation and heptane (41.52 kg)
  4. additionadded
  5. additionfollowed by the addition of heptane (48.6 kg)
  6. filtrationthe solution filtered through a Celite® (4.08 kg) bed at 40° C.
  7. washthe cake washed twice with heptane (7.2 kg)
  8. waitto −12° C. over 5 hrs
  9. waitheld for 12 hrs at −12° C
  10. filtrationThe suspension was filtered
  11. washthe cake washed with cold (0° C.) heptane (8.5 kg)
  12. customdryed at 25° C. under vacuum, which

出典と根拠

ORDレコード
ord-8f2b07b46dc8480a809bb84a2d0b7864
出典データセット
uspto-grants-2012_01
特許番号
US08101750B2

反応ノート

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