Hydrochloric Acid → HCID 178421864, compound

HRID 1760474Notes

Reaction equation

HRID 1760474 reaction equation
CN(C)S([N:6]1[C:10]([CH2:11][C:12]2[CH:21]=[CH:20][C:15]3[O:16][CH2:17][CH2:18][O:19][C:14]=3[CH:13]=2)=[C:9](C)[N:8]=[CH:7]1)(=O)=O.Cl.[C:25](=O)(O)[O-].[Na+]>C(OCC)(=O)C>[O:16]1[C:15]2[CH:20]=[CH:21][C:12]([CH2:11][C@@:10]3([CH3:25])[CH2:9][NH:8][CH:7]=[N:6]3)=[CH:13][C:14]=2[O:19][CH2:18][CH2:17]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 207117805-(2,3-Dihydrobenzo[1,4]dioxin-6-ylmethyl)-4-methylimidazole-1-sulfonic acid dimethylamide

Product 1

HCID 178421864HCID 178421864, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-Methyl-1-(dimethylsulfamoyl)imidazole (1) (2.0 g, 10.6 mmol) is taken up in 42 mL of anhydrous THF and cooled to −78° C. n-BuLi (6.6 mL, 10.6 mmol) is added dropwise to the solution of (1). The resultant solution is stirred at −78° C. for 30 min. Tert-butyldimethylsilylchloride (TBSCl) (1.6 g, 10.6 mmol) in 10 mL of THF is added to the reaction. The reaction is warmed to rt and stirred overnight. The next day the reaction is cooled to −20° C. and 7.3 mL (11.6 mmol) of n-BuLi added. After stirring at −20° C. for 30 min, 1,4-benzodioxan-6-carboxaldehyde (2) (1.92 g, 11.7 mmol) in 10 mL of THF is added to the reaction mixture. Then reaction is warmed to rt and stirred for 3 h. The reaction is quenched with water and diluted with ethyl acetate. The organic layer is washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (1:2 ethyl acetate/hexane) affords 3.9 g (8.4 mmol) of 2-(t-butyldimethylsilyl)-5-[(2,3-dihydro benzo[1,4]dioxin-6-yl)hydroxymethyl]-4-methylimidazole-1-sulfonic acid dimethylamide (3). (3) (1.0 g, 2.14 mmol) is taken up in 21 mL of THF. A 1M solution of tetra-n-butylammonium fluoride (TBAF) in THF (2.35 mL, 2.35 mmol) is added dropwise to the solution of (3). The reaction is stirred for 30 min at rt. The reaction is quenched with water and then extracted with ethyl acetate. The organic layer is washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography using ethyl acetate as eluant affords 0.75 g (2.12 mmol) 5-[(2,3-dihydrobenzo[1,4]dioxin-6-yl)hydroxymethyl]-4-methylimidazole-1-sulfonic acid dimethylamide (4). (4) (0.75 g, 2.12 mmol) is taken up in 28 mL of dichloromethane, to the solution is added 2.7 mL (17.0 mmol) of triethylsilane and 5.2 mL (67.8 mmol) of trifluoroacetic acid. The reaction is stirred at rt overnight and then quenched with water and neutralized with solid sodium bicarbonate. The organic layer is washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography using a 3:1 mixture of ethyl acetate and hexane affords 0.63 g (1.87 mmol) of 5-(2,3-dihydrobenzo[1,4]dioxin-6-ylmethyl)-4-methylimidazole-1-sulfonic acid dimethylamide (5). (5) (0.63 g, 1.87 mmol) is taken up in 10 mL of a 1.5N HCl solution and heated at reflux for. The reaction is diluted with ethyl acetate, neutralized with solid sodium bicarbonate. The organic layer is washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Crystallization from ether/hexane affords 0.33 g (1.43 mmol) of 4(5)-(2,3-dihydrobenzo[1,4]dioxin-6-ylmethyl)-4-methyl-1H-imidazole (6) (M).

Workup

  1. temperatureheated
  2. temperatureat reflux for
  3. washThe organic layer is washed with water
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. customthe solvent removed under reduced pressure
  6. customCrystallization from ether/hexane

Sources & evidence

ORD record
ord-0e2e45773a7640b4b891bd779ab0a542
Source dataset
uspto-grants-2005_01
Patent number
US06841684B2

Reaction notes

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