Hydrochloric Acid → 4-(5-Amino-1-methyl-1H-benzoimidazol-2-yl)-butyric acid methyl ester hydrochloride

HRID 1967483ノート

反応式

HRID 1967483 の反応式
[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][C:7](=O)[N:8]([C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][C:11]=1[N+:19]([O-])=O)[CH3:9].[H][H].[ClH:26]>[Pd].CO>[ClH:26].[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][C:7]1[N:8]([CH3:9])[C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:11]=2[N:19]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 583828074-[(2,4-Dinitro-phenyl)-methyl-carbamoyl]-butyric acid methyl esterHCID 178418361HCID 178418361、化合物

生成物 1

HCID 468993894-(5-Amino-1-methyl-1H-benzoimidazol-2-yl)-butyric acid methyl ester hydrochloride収率 92%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

実験手順

A one-liter Buchi reactor was charged with 20 grams of 4-[(2,4-dinitro-phenyl)-methyl-carbamoyl]-butyric acid methyl ester, 1.0 g of palladium on carbon (dry basis, 10% Pd), and 180 mL of methanol at ambient temperature. The resulting mixture was subjected to hydrogenation at 40 psi overnight (ca. 18 hours) with a hydrogen mass transfer coefficient (kLa) of 0.12 to 0.28. The reaction mixture was filtered through a thin pad of Celite® 540. To the filtrate was added 2.8 mL of concentrated hydrochloric acid (1.1 eq vs. starting material). The resulting mixture was stirred under reflux for 3.5 hours. Approximately ¾ amount of solvent was removed under reduced pressure. Then warm tetrahydrofuran (THF) (150 mL) was added while vigorously stirring. The precipitate was collected by filtration and dried overnight under vacuum to afford a coffee-colored solid (16.1 g, yield 92%) with a purity of 98 Area % by HPLC analysis (HPLC Method B). 1H NMR (400 MHz, DMSO-d6) δ 7.83 (d, J=8.8 Hz, 1H), 7.50 (s, 1H), 7.27 (d, J=8.6 Hz, 1H), 3.91 (s, 3H), 3.58 (s, 3H), 3.17 (t, J=7.7 Hz, 2H), 2.53 (t, J=7.3 Hz, 2H, overlapped partially with DMSO), 2.07 (quint, J=7.5 Hz, 2H); LC/MS (ESI, m/z) 248 (M+1).

後処理

  1. filtrationThe reaction mixture was filtered through a thin pad of Celite® 540
  2. temperatureunder reflux for 3.5 hours
  3. customApproximately ¾ amount of solvent was removed under reduced pressure
  4. additionThen warm tetrahydrofuran (THF) (150 mL) was added
  5. stirringwhile vigorously stirring
  6. filtrationThe precipitate was collected by filtration
  7. customdried overnight under vacuum

出典と根拠

ORDレコード
ord-d7f91b5c48a74d149df3fe1f9495d8d1
出典データセット
uspto-grants-2013_04
特許番号
US08420829B2

反応ノート

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