Dimethyl Sulfate → N-Formyl-2-methoxy-N-methyl-alpha-(3-methyl-2-thienyl)benzeneethanamine

HRID 486692Notes

Reaction equation

HRID 486692 reaction equation
[CH:1]([N:3]([CH3:19])[CH:4]([C:13]1[S:14][CH:15]=[CH:16][C:17]=1[CH3:18])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[OH:12])=[O:2].[CH3:20]C(C)([O-])C.[K+].COS(OC)(=O)=O>O1CCCC1>[CH:1]([N:3]([CH3:19])[CH:4]([C:13]1[S:14][CH:15]=[CH:16][C:17]=1[CH3:18])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][CH3:20])=[O:2]

Participants

5

Reactant 3

HCID 6497Dimethyl Sulfate2×HCID 22414398N-formyl-2-hydroxy-N-methyl-alpha-(3-methyl-2-thienyl)benzeneethanamineHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 22414408N-Formyl-2-methoxy-N-methyl-alpha-(3-methyl-2-thienyl)benzeneethanamineYield 65.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-water chilled solution of 5.10 g of N-formyl-2-hydroxy-N-methyl-α-(3-methyl-2-thienyl)benzeneethanamine and 100 ml of tetrahydrofuran, was added 2.24 g of potassium t-butoxide and then a solution of 2.52 g of dimethylsulfate and 25 ml of tetrahydrofuran dropwise, with stirring. The mixture was stirred at ice-bath temperature for 30 min, at room temperature for one hr, and at reflux for 30 mins. Additional dimethylsulfate and potassium t-butoxide were added and the mixture was refluxed for 20 min. The reaction mixture was decanted into 40 ml of water and basified with 10% sodium hydroxide solution. The mixture was extracted with dichloromethane. The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was combined with a previous sample. The combined residue was purified by preparative HPLC (Water Associates Prep LC/System 500, silica gel, material applied as a solution in dichloromethane, eluted with ethyl acetate-hexane (1:1, 200 ml/min flow rate). The appropriate fractions were combined and concentrated. The residue crystallized during refrigerated storage. Recrystallization from cyclohexane afforded 3.5 g of the product, mp 80°-83° C.

Workup

  1. waitat room temperature for one hr
  2. temperatureat reflux for 30 mins
  3. temperaturethe mixture was refluxed for 20 min
  4. customThe reaction mixture was decanted into 40 ml of water and basified with 10% sodium hydroxide solution
  5. extractionThe mixture was extracted with dichloromethane
  6. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe combined residue was purified by preparative HPLC (Water Associates Prep LC/System 500, silica gel, material
  10. washeluted with ethyl acetate-hexane (1:1, 200 ml/min flow rate)
  11. concentrationconcentrated
  12. customThe residue crystallized during refrigerated storage
  13. customRecrystallization from cyclohexane

Sources & evidence

ORD record
ord-3f4e4c4ab6284d418a0973405bc6f09a
Source dataset
uspto-grants-1994_03
Patent number
US05292760

Reaction notes

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