Hydrochloric Acid → Ethyl 2-methoxy-5-morpholin-4-ylmethyl-benzimidate hydrochloride

HRID 1167329Notes

Reaction equation

HRID 1167329 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:8][C:5]=1[C:6]#[N:7].[CH2:19]([OH:21])[CH3:20]>>[ClH:1].[CH3:2][O:3][C:4]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:8][C:5]=1[C:6](=[NH:7])[O:21][CH2:19][CH3:20]

Participants

4

Reactant 3

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 229962172-Methoxy-5-morpholin-4-ylmethyl-benzonitrile

Product 1

HCID 22996248Ethyl 2-methoxy-5-morpholin-4-ylmethyl-benzimidate hydrochloride

Procedure

Hydrogen chloride gas was passed through a solution of 2-methoxy-5-morpholin-4-ylmethyl-benzonitrile (300 mg, 1.292 mmol) in anhydrous ethanol (30 mL) at room temperature. After 2 h, hydrogen chloride gas was stopped and the reaction vessel was sealed. After stirring at room temperature for 12 h, the reaction vessel was cooled to 0° C. and opened. The solvent was evaporated in vacuo to dryness to afford crude ethyl 2-methoxy-5-morpholin-4-ylmethyl-benzimidate hydrochloride. meso-1,2-Bis-(4-chloro-phenyl)-ethane-1,2-diamine (150 mg, 0.533 mmol), triethylamine (373 μL, 5 mmol) and ethanol (10 mL) were added and the resulting mixture was heated at reflux for 12 h. The solvent was removed and the residue was taken up in methylene chloride (2 mL) and sodium bicarbonate solution (2 mL). The product was extracted with methylene chloride (2×30 mL). The organic layers were washed with brine (1×5 mL) and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 0-20% methanol in ethyl acetate to afford 4-{3-[4,5-bis-(4-chloro-phenyl)-4,5-dihydro-1H-imidazol-2-yl]-4-methoxy-benzyl}-morpholine (164 mg, 62%). LR-MS (APCI): 496 [(M+H)+].

Workup

  1. customthe reaction vessel was sealed
  2. temperaturethe reaction vessel was cooled to 0° C.
  3. customThe solvent was evaporated in vacuo to dryness

Sources & evidence

ORD record
ord-b7d255a1c59c4f9b9dc3aec858996f81
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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