Diazomethane → HCID 23343224, compound

HRID 27620Notes

Reaction equation

HRID 27620 reaction equation
[N+](=[CH2:3])=[N-].[CH:4]([C:7]1[N:8]([S:16]([C:19]2[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[C:9]([CH2:12][C:13](Cl)=[O:14])=[CH:10][N:11]=1)([CH3:6])[CH3:5].C1C=CN=CC=1.[FH:32]>CCOCC>[F:32][CH2:3][C:13]([CH2:12][C:9]1[N:8]([S:16]([C:19]2[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[C:7]([CH:4]([CH3:6])[CH3:5])=[N:11][CH:10]=1)=[O:14]

Participants

5

Reactant 3

HCID 9550DiazomethaneHCID 64774Pyridine, hydrofluoride (1:1)HCID 867372052-Isopropyl-1-tosylimidazol-5-ylacetyl chloride

Product 1

HCID 23343224HCID 23343224, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

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. stirringAfter stirring for 11/2 hours at 25° C. the reaction mixture
  2. customprecooled to 0° C
  3. stirringThe resulting heterogeneous solution is stirred at 25° C. for 11/2 hours
  4. customThe organic phase is separated
  5. washwashed with sodium bicarbonate (pH of 8)
  6. dry with materialwith brine and dried over magnesium sulfate

Sources & evidence

ORD record
ord-a41781af9a584378860face6df7e00f1
Source dataset
uspto-grants-1980_09
Patent number
US04221914

Reaction notes

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