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 1161769Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1161769
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]

Komponenten

6

Edukt 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

Produkt 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 esterAusbeute 38,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-fd5d213a2d9e4d92b66a91f6a3698800
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07820659B2

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