Toluene → Methyl 6-amino-4-(chroman-6-yl)-5-(hydroxymethyl)-2-methylnicotinate

HRID 1912543ノート

反応式

HRID 1912543 の反応式
COCCO[AlH2-]OCCOC.[Na+].C1(C)C=CC=CC=1.[NH2:20][C:21]1[C:26]([C:27](OCC)=[O:28])=[C:25]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[O:38][CH2:37][CH2:36][CH2:35]3)[C:24]([C:42]([O:44][CH3:45])=[O:43])=[C:23]([CH3:46])[N:22]=1>O1CCCC1>[NH2:20][C:21]1[C:26]([CH2:27][OH:28])=[C:25]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[O:38][CH2:37][CH2:36][CH2:35]3)[C:24]([C:42]([O:44][CH3:45])=[O:43])=[C:23]([CH3:46])[N:22]=1

参加物

5

反応物 3

HCID 1140TolueneHCID 16684438Red-AlHCID 712092193-Ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylate

生成物 1

HCID 71209315Methyl 6-amino-4-(chroman-6-yl)-5-(hydroxymethyl)-2-methylnicotinate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

An ice cooled solution of Red-Al, 65 wt % solution in toluene (12.58 mL, 41.3 mmol) in tetrahydrofuran (THF) (188 mL) was treated with a solution of 3-ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylate (7.64 g, 20.63 mmol) in tetrahydrofuran (THF) (31.4 mL) and the mixture was stirred at 0° C. for 5 minutes. The mixture was quenched with water (32 mL) then 15% NaOH (16 mL) was added. The mixture was warmed to ambient temperature and stirred for 20 minutes (solids formed). The mixture was filtered and then filtrate was concentrated. The residue was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and then concentrated to afford the crude methyl 6-amino-4-(chroman-6-yl)-5-(hydroxymethyl)-2-methylnicotinate as a light brown solid which was used without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 6.87-6.72 (m, 3 H), 5.35-5.19 (m, 2 H), 4.50-4.41 (m, 2 H), 4.25-4.18 (m, 2 H), 3.50-3.45 (m, 3 H), 2.78 (t, J=6.4 Hz, 2 H), 2.38 (s, 3 H), 2.06-2.00 (m, 2 H); LC/MS (m/z) ES+=329.26 (M+1).

後処理

  1. customThe mixture was quenched with water (32 mL)
  2. addition15% NaOH (16 mL) was added
  3. temperatureThe mixture was warmed to ambient temperature
  4. stirringstirred for 20 minutes
  5. custom(solids formed)
  6. filtrationThe mixture was filtered
  7. concentrationfiltrate was concentrated
  8. additionThe residue was diluted with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-4d4e9ef27f0f485eac318ec66e0cbb47
出典データセット
uspto-grants-2013_12
特許番号
US08609653B2

反応ノート

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