Trimethyl orthoacetate → HCID 86672707, compound

HRID 2369906Notes

Reaction equation

HRID 2369906 reaction equation
[NH2:1][C:2]1[C:3]([NH:12][CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:19](OC)(OC)(OC)[CH3:20]>CN(C=O)C>[CH3:16][O:15][CH:14]([O:17][CH3:18])[CH2:13][N:12]1[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=2[N:1]=[C:19]1[CH3:20]

Participants

4

Reactant 2

HCID 15050Trimethyl orthoacetateHCID 66889618HCID 66889618, compound

Product 1

HCID 86672707HCID 86672707, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 3-amino-2-(2,2-dimethoxyethylamino)benzoate (1.0 g, 3.9 mmol) from Step C of Example 13 in DMF (30 mL) was added trimethyl orthoacetate (1.5 mL, 11.8 mmol) and the reaction was refluxed overnight. The reaction mixture was washed with saturated aqueous sodium bicarbonate, extracted with methylene chloride, dried (Na2SO4), filtered, and concentrated under reduced pressure to give the crude material which was purified by column chromatography (silica gel, 0% to 90% ethyl acetate in hexanes) to afford methyl 1-(2,2-dimethoxyethyl)-2-methyl-1H-benzo[d]imidazole-7-carboxylate (0.8 g, 72%): 1H NMR (300 MHz, DMSO-d6) δ 7.74 (dd, J=8.1, 1.2 Hz, 1H), 7.55 (dd, J=7.8, 1.2 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 4.56 (d, J=4.8 Hz, 2H), 4.44 (t, J=4.8 Hz, 1H), 3.90 (s, 3H), 3.21 (s, 6H), 2.58 (s, 3H); MS (ESI+) m/z 279 (M+H).

Workup

  1. temperaturethe reaction was refluxed overnight
  2. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate
  3. extractionextracted with methylene chloride
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude material which
  8. customwas purified by column chromatography (silica gel, 0% to 90% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-eac20bc302164136949908f0e8ca8b6d
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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