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 1161769노트

반응식

HRID 1161769 반응식
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]

참가 물질

6

반응물 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

생성물 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 ester수율 38.4%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-fd5d213a2d9e4d92b66a91f6a3698800
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820659B2

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