Methanol → N-(2,4-dimethoxybenzyl)thiazol-2-amine

HRID 1619692Notes

Reaction equation

HRID 1619692 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[NH2:13][C:14]1[S:15][CH:16]=[CH:17][N:18]=1.[BH4-].[Na+].CO>ClC(Cl)C.N1CCCCC1>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH2:5][NH:13][C:14]1[S:15][CH:16]=[CH:17][N:18]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 21552-AminothiazoleHCID 691752,4-DimethoxybenzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineYield 64%

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

2,4-Dimethoxybenzaldehyde (25 g, 150 mmol), 2-aminothiazole (15.1 g, 150 mmol) and piperidine (150 mg, 1.76 mmol) were combined in dichloroethane (500 ml) and the mixture was heated to reflux over 4 Å molecular sieves for 18 hours. The sieves were removed by filtration and the reaction mixture diluted with methanol (300 ml). Sodium borohydride (25 g, 662 mmol) was added in portions and the reaction mixture heated to reflux for 2 hours. The cooled reaction mixture was quenched with water (50 mL) and the organic solvents evaporated in vacuo. The aqueous residue was extracted with ethyl acetate (2×100 mL) and the combined organic solutions extracted with 2M HCl (2×50 mL). The acidic solution was basified with solid potassium carbonate and re-extracted with ethyl acetate (2×50 mL). The organic layer was dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography eluting with 9:1 dichloromethane:methanol to yield the title compound (24 g, 96 mmol, 64%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux over 4 Å molecular sieves for 18 hours
  3. customThe sieves were removed by filtration
  4. additionthe reaction mixture diluted with methanol (300 ml)
  5. temperaturethe reaction mixture heated
  6. temperatureto reflux for 2 hours
  7. customThe cooled reaction mixture
  8. customwas quenched with water (50 mL)
  9. customthe organic solvents evaporated in vacuo
  10. extractionThe aqueous residue was extracted with ethyl acetate (2×100 mL)
  11. extractionthe combined organic solutions extracted with 2M HCl (2×50 mL)
  12. extractionre-extracted with ethyl acetate (2×50 mL)
  13. dry with materialThe organic layer was dried over Na2SO4
  14. filtrationfiltered
  15. customevaporated in vacuo
  16. customThe residue was purified by column chromatography
  17. washeluting with 9:1 dichloromethane

Sources & evidence

ORD record
ord-acfb7159bc774d0aa649cbc32467c7ce
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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