Hydrochloric Acid → [2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanol

HRID 1521423Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1521423
C[O:2][C:3]([C:5]1[CH:20]=[CH:19][C:8]2[N:9]([CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])[C:10]([Cl:12])=[N:11][C:7]=2[CH:6]=1)=O.C1(NC(C2C=CC3NC(N4C=C(C(O)=O)C=N4)=NC=3C=2)=O)C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O.C1COCC1>[Cl:12][C:10]1[N:9]([CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])[C:8]2[CH:19]=[CH:20][C:5]([CH2:3][OH:2])=[CH:6][C:7]=2[N:11]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 21226445Aluminium lithium hydrideHCID 669372622-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl esterHCID 1785248161-(5-phenylcarbamoyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid

Produkt 1

HCID 66937356[2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanolAusbeute 78,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a stirred solution of 2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester (Intermediate from EXAMPLE 120, product of Step C) (0.500 g, 1.67 mmol) and THF (30 mL) was added lithium aluminum hydride (2M in THF, 0.836 mL) dropwise over 10 min at 0° C. The reaction mixture was stirred for 48 h, warming to 23° C. The reaction mixture was cooled to 0° C. water (20 mL) was added and the resulting mixture was acidified with 1M HCl. The product was extracted with EtOAc (3×40 mL) and the combined organic layers were washed with brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (5-80% EtOAc/hexanes) to yield the titled compound (0.356 g, 78%) as a 1:1 mixture of regioisomers. MS (ESI/CI): mass calcd. for C12H15ClN2O3, 270.1; m/z found, 271.1 [M+H]+. 1H (600 MHz, CDCl3): 7.65-7.61 (m, 2H), 7.52 (s, J=0.7 Hz, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.35 (dd, J=8.3 Hz, 1.5 Hz, 1H), 7.27 (dd, J=8.2 Hz, 1.5 Hz, 1H), 5.63 (s, 2H), 5.62 (s, 2H), 4.81 (s, 2H), 4.77 (s, 2H), 3.64-3.60 (m, 4H), 3.49 (dd, J=5.4 Hz, 3.6 Hz, 4H), 3.35 (s, 3H), 3.34 (s, 3H), 2.59 (s, 1H), 2.50 (s, 1H).

Aufarbeitung

  1. additionwas added
  2. extractionThe product was extracted with EtOAc (3×40 mL)
  3. washthe combined organic layers were washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified (FCC) (5-80% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-9ff99a1290834414b0ae46e6155fc022
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073923B2

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