1-(Chloromethoxy)-2-methoxyethane → 2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester

HRID 408748Notes

Reaction equation

HRID 408748 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:8]2[NH:9][C:10]([Cl:12])=[N:11][C:7]=2[CH:6]=1)=[O:4].CCN(C(C)C)C(C)C.Cl[CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:8]2[N:9]([CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])[C:10]([Cl:12])=[N:11][C:7]=2[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 81531DiisopropylethylamineHCID 178497361HCID 178497361, compound

Product 1

HCID 669372622-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-chloro-1H-benzoimidazole-5-carboxylic acid methyl ester (2.00 g, 9.50 mmol) and THF (17 mL) was added DIPEA (2.46 mL, 14.3 mmol) followed by 1-chloromethoxy-2-methoxy-ethane (1.30 mL, 11.4 mmol) at 23° C. After stirring for 18 h the reaction mixture was concentrated under reduced pressure. The residue was purified (FCC) (5-50% EtOAc/hexanes) to yield the titled compound as a mixture of regioisomers (1.71 g, 60%). MS (ESI/CI): mass calcd. for C13H15ClN2O4, 298.1; m/z found, 299.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 8.34-8.31 (m, 1H), 8.21-8.20 (m, 1H), 7.98 (dd, J=8.6, 1.6 Hz, 1H), 7.91 (dd, J=8.5, 1.6 Hz, 1H), 7.83 (dd, J=8.6, 0.5 Hz, 1H), 7.74 (dd, J=8.5, 0.5 Hz, 1H), 5.78 (s, 1H), 5.73 (s, 1H), 3.89 (d, J=6.3 Hz, 6H), 3.64-3.60 (m, 5H), 3.43-3.39 (m, 5H), 3.17 (d, J=2.6 Hz, 6H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was purified (FCC) (5-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e0dc9ade7ed54bf8a7bbe95427319e4a
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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