Anisole → HCID 178446265, compound

HRID 1066171Notes

Reaction equation

HRID 1066171 reaction equation
O1[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:6]1(OC)C=CC=CC=1.[Cl:14][C:15]1[CH:28]=[CH:27][C:18]2[NH:19][C:20](=O)[N:21]([CH3:25])[S:22](=[O:24])(=O)[C:17]=2[CH:16]=1.[OH-:29].[NH4+:30]>CC(N)C(C)C.C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(C)C>[Cl:14][C:15]1[CH:28]=[CH:27][C:18]2[N:30]=[C:20]([NH:19][CH:4]([CH3:5])[CH:3]([CH3:6])[CH3:2])[N:21]([CH3:25])[S:22](=[O:24])(=[O:29])[C:17]=2[CH:16]=1

Participants

9

Reactant 4

HCID 7519AnisoleHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 21197878HCID 21197878, compound

Product 1

HCID 178446265HCID 178446265, compound

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 117311,2-DimethylpropylamineSolvent3×

Conditions

Temperature
120 °C

Procedure

To 10 ml of dry tetrahydrofuran stirred under nitrogen was added successively titanium tetrachloride (0.2 ml), anisole (0.5 ml), 1,2-dimethylpropylamine (0.8 ml), and then a slurry of 7-chloro-2,3-dihydro-2-methyl-3-oxo-4H-1,2,4-benzothiadiazine 1,1-dioxide (400 mg) in a mixture of 1,2-dimethylpropylamine (0.4 ml) and 5 ml of dry toluene. The mixture was heated at 120° C. After 1½ h an additional amount of 1,2-dimethylpropylamine (0.4 ml) was added. After 2½ h the reaction mixture was cooled to room temperature. Isopropyl alcohol (1 ml), concentrated ammonium hydroxide (1 ml) and diatomaceous earth (0.5 g) was added and stirring was continued for 15 min. The insoluble material was removed by filtration and the filter cake rinsed with two portions of 25 ml of ethyl acetate. The organic phases were combined and shaken with 25 ml of water, then with 25 ml of saturated aqueous sodium chloride, dried over sodium sulfate and the solvent was removed in vacuo. The residue was dissolved in 50 ml of ethyl acetate and extracted with 2×50 ml of 4 M hydrochloric acid. The aqueous extracts were made alkaline with concentrated ammonium hydroxide and then extracted with 2×50 ml of ethyl acetate. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. The residue was purified on a silica gel column with a 7:3 mixture of n-heptane and ethyl acetate as solvent to give the title compound as white crystals; m.p. 102-105° C.

Workup

  1. temperatureAfter 2½ h the reaction mixture was cooled to room temperature
  2. customThe insoluble material was removed by filtration
  3. washthe filter cake rinsed with two portions of 25 ml of ethyl acetate
  4. stirringshaken with 25 ml of water
  5. dry with materialwith 25 ml of saturated aqueous sodium chloride, dried over sodium sulfate
  6. customthe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in 50 ml of ethyl acetate
  8. extractionextracted with 2×50 ml of 4 M hydrochloric acid
  9. extractionextracted with 2×50 ml of ethyl acetate
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. customthe solvent removed in vacuo
  12. customThe residue was purified on a silica gel column with a 7:3 mixture of n-heptane and ethyl acetate as solvent

Sources & evidence

ORD record
ord-8827bf5fe4f24ed7a7de28610e7733f9
Source dataset
uspto-grants-2001_06
Patent number
US06242443B1

Reaction notes

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