Hydrochloric Acid → 2-Isopropyl-1-tosylimidazol-5-ylacetic acid

HRID 27618Notes

Reaction equation

HRID 27618 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl.[CH:8]([C:11]1[NH:12][C:13]([CH2:16][C:17]([OH:19])=[O:18])=[CH:14][N:15]=1)([CH3:10])[CH3:9].[S:20](Cl)([C:23]1[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=1)(=[O:22])=[O:21].Cl>O.C(OCC)(=O)C>[CH:8]([C:11]1[N:12]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[C:13]([CH2:16][C:17]([OH:19])=[O:18])=[CH:14][N:15]=1)([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 10340Sodium CarbonateHCID 70591476HCID 70591476, compound

Product 1

HCID 538449612-Isopropyl-1-tosylimidazol-5-ylacetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To 200 ml of cold thionyl chloride is added 0.1 mole of 3-isopropylimidazol-5-ylmethanol. After stirring for 1 hour at 25° C. the excess thionyl chloride is evaporated under reduced pressure to give crude 5-chloromethyl-2-isopropylimidazole hydrochloride. To an ice cold solution of 5 mmole of 5-chloromethyl-2-isopropylimidazole hydrochloride in 25 ml of dry dimethylformamide is added a cold solution of powdered sodium cyanide (18 mmole) in 30 ml of dimethylformamide. The mixture is stirred overnight at 25° C. then diluted with 200 ml of water and neutralized with sodium bicarbonate. The solution is saturated with sodium chloride and extracted with ethylacetate (5×50 ml). The organic extracts are washed with water, dried over magnesium sulfate and evaporated under reduced pressure to give a solid residue which is sublimed to give 5-cyanomethyl-2-isopropylimidazole. 5-cyanomethyl-2-isopropylimidazole (10 mmole) is heated with 10 ml of concentrated hydrochloric acid for 12 hours at reflux temperature then concentrated under reduced pressure to give 2-isopropylimidazol-5-ylacetic acid hydrochloride. To an ice cold solution of 0.08 mole of sodium carbonate in 40 ml of water is added 2-isopropylimidazol-5-ylacetic acid hydrochloride followed by 0.025 mole of tosyl chloride dissolved in 30 ml of ethyl acetate. After stirring for 5 hours at 25° C. the reaction mixture is neutralized with hydrochloric acid M and extracted with ethyl acetate. The organic phase is washed with water, dried over magnesium sulfate and concentrated under reduced pressure to yield 2-isopropyl-1-tosylimidazol-5-ylacetic acid. To a suspension of the sodium salt of 2-isopropyl-1-tosylimidazol-5-ylacetic acid in 100 ml of benzene is added 1 equivalent of oxalyl chloride. The reaction mixture is stirred at 25° C. for 12 hours. The precipitate is filtered off and the filtrate concentrated under reduced pressure to give 2-isopropyl-1-tosylimidazol-5-ylacetyl chloride. To a solution of 29 mmole of diazomethane in 84 ml of ether cooled to 0° C. and magnetically stirred is added dropwise over 45 minutes a solution of 14.3 mmole of 2-isopropyl-1-tosylimidazol-5-ylacetyl chloride in 60 ml of ether. After stirring for 11/2 hours at 25° C. the reaction mixture is added to a solution of hydrogen fluoride/pyridine precooled to 0° C. The resulting heterogeneous solution is stirred at 25° C. for 11/2 hours then poured onto 150 g of ice. The organic phase is separated, washed with sodium bicarbonate (pH of 8) then with brine and dried over magnesium sulfate. Concentration of the mixture under reduced pressure yields 2-isopropyl-1-tosylimidazol-5-ylmethyl fluoromethyl ketone.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase is washed with water
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-243c1776724543b998c6823d9ee52460
Source dataset
uspto-grants-1980_09
Patent number
US04221914

Reaction notes

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