Acetic Acid → 3-(4-Benzyloxy-2,6-dichloro-benzyl)-2-oxo-1-(4,5,6,7-tetrahydro-3H-benzoimidazol-5-yl)-pyrrolidine-3-carboxylic acid ethyl ester

HRID 1161769ノート

反応式

HRID 1161769 の反応式
C([BH3-])#N.[Na+].C([O:7][C:8](=O)[C:9]([CH2:18][C:19]1[C:24]([Cl:25])=[CH:23][C:22]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:21][C:20]=1[Cl:34])([CH2:15][CH:16]=O)[C:10]([O:12][CH2:13][CH3:14])=[O:11])C.Cl.Cl.[N:38]1[C:42]2[CH2:43][CH2:44][CH:45]([NH2:47])[CH2:46][C:41]=2[NH:40][CH:39]=1.C(O)(=O)C>CO>[CH2:13]([O:12][C:10]([C:9]1([CH2:18][C:19]2[C:20]([Cl:34])=[CH:21][C:22]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:23][C:24]=2[Cl:25])[CH2:15][CH2:16][N:47]([CH:45]2[CH2:44][CH2:43][C:42]3[N:38]=[CH:39][NH:40][C:41]=3[CH2:46]2)[C:8]1=[O:7])=[O:11])[CH3:14]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 686481735-Amino-4,5,6,7-tetrahydrobenzimidazole dihydrochlorideHCID 866291152-(4-Benzyloxy-2,6-dichloro-benzyl)-2-(2-oxo-ethyl)-malonic acid diethyl ester

生成物 1

HCID 686483313-(4-Benzyloxy-2,6-dichloro-benzyl)-2-oxo-1-(4,5,6,7-tetrahydro-3H-benzoimidazol-5-yl)-pyrrolidine-3-carboxylic acid ethyl ester収率 38.4%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
60 °C

実験手順

Add sodium cyanoborohydride (3.6 g, 57.4 mmol) portion wise to a solution of 2-(4-benzyloxy-2,6-dichloro-benzyl)-2-(2-oxo-ethyl)-malonic acid diethyl ester (6.7 g, 14.4 mmol) (Preparation 10) and 4,5,6,7-tetrahydro-3H-benzoimidazol-5-ylamine dihydrochloride salt (6.0 g, 28.7 mmol) (Preparation 1) in 70 ml of Methanol. After 3 h, add 4 ml of acetic acid and warm to 60° C. for 16 h. Most of the Methanol is removed via rotovap. Quench the resulting mixture with saturated bicarbonate and extract with ethyl acetate. Dry extracts over sodium sulfate, concentrate, and purify by normal phase column chromatography (0-10% methanol in ethyl acetate) to afford 3-(4-Benzyloxy-2,6-dichloro-benzyl)-2-oxo-1-(4,5,6,7-tetrahydro-3H-benzoimidazol-5-yl)-pyrrolidine-3-carboxylic acid ethyl ester as a white solid (3 g).

後処理

  1. customMost of the Methanol is removed via rotovap
  2. customQuench the resulting mixture with saturated bicarbonate
  3. extractionextract with ethyl acetate
  4. customDry
  5. concentrationconcentrate
  6. custompurify by normal phase column chromatography (0-10% methanol in ethyl acetate)

出典と根拠

ORDレコード
ord-fd5d213a2d9e4d92b66a91f6a3698800
出典データセット
uspto-grants-2010_10
特許番号
US07820659B2

反応ノート

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