7-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester → 3-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid

HRID 338771ノート

反応式

HRID 338771 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([O:23]C(C)(C)C)=[O:22])[CH:16]=3)[CH2:10][C:9]=2[CH:8]=[N:7][CH:6]=1)=[O:4]>C(O)=O>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]2[C:14]=1[CH2:13][CH2:12][N:11]([C:15]1[CH:16]=[C:17]([CH:18]=[CH:19][CH:20]=1)[C:21]([OH:23])=[O:22])[CH2:10]2)=[O:4]

参加物

3

反応物 1

HCID 866958807-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester

生成物 1

HCID 866958813-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid収率 66%

試薬・触媒・溶媒 1

HCID 284Formic Acid溶媒

反応条件

温度
30 °C

実験手順

A mixture of 7-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester (6.9 g, 0.0188 mol) and 98% formic acid (30 mL) was heated at 50° C. for 4 hr and at 30° C. overnight. HPLC analysis showed the reaction was not complete. It was heated at 50° C. for an additional 1.5 hr. The reaction mixture was concentrated under reduced pressure. Diluted with dichloromethane (200 mL) and cooled to 0° C. To the mixture (liquid and solid) was added saturated sodium bicarbonate until to get a pH=5-6 at 0° C. The solid was collected, washed with water (50 mL), dichloromethane (50 mL) and air dried. The solid was triturated with acetone (50 mL) for 30 min. The yellow-green solid was collected and dried in a drying pistol with refluxing acetone overnight to give the title compound (3.86 g, 66%). 1H NMR 300 MHz (d6-DMSO), δ 13 (brs, 1H), 8.8 (s, 1H), 8.65 (s, 1H), 7.5 (m, 4H), 4.5 (s, 2H), 3.8 (s, 3H), 3.6 (t, 2H), 3.2 (t, 2H).

後処理

  1. temperatureIt was heated at 50° C. for an additional 1.5 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionDiluted with dichloromethane (200 mL)
  4. temperaturecooled to 0° C
  5. additionTo the mixture (liquid and solid) was added saturated sodium bicarbonate until
  6. customto get a pH=5-6 at 0° C
  7. customThe solid was collected
  8. washwashed with water (50 mL), dichloromethane (50 mL) and air
  9. customdried
  10. customThe solid was triturated with acetone (50 mL) for 30 min
  11. customThe yellow-green solid was collected
  12. dry with materialdried in a drying pistol with refluxing acetone overnight

出典と根拠

ORDレコード
ord-f896782e415e44798a4142d73465c34f
出典データセット
uspto-grants-2014_11
特許番号
US08889870B2

反応ノート

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