N-Methyltyramine → 2-Bromo-5-hydroxy-N-[2-(4-hydroxyphenyl)ethyl]-4-methoxy-N-methylbenzamide

HRID 1015921Notes

Reaction equation

HRID 1015921 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([OH:13])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH3:14][NH:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1>ClCCl>[CH3:14][N:15]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[C:4]([C:3]1[CH:7]=[C:8]([OH:13])[C:9]([O:11][CH3:12])=[CH:10][C:2]=1[Br:1])=[O:5]

Participants

4

Reactant 2

HCID 9727N-MethyltyramineHCID 441396432-Bromo-5-hydroxy-4-methoxy benzoyl chloride

Product 1

HCID 4437382-Bromo-5-hydroxy-N-[2-(4-hydroxyphenyl)ethyl]-4-methoxy-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

The previously prepared 2-bromo-5-hydroxy-4-methoxy benzoyl chloride (B13-Cl) in dichloromethane solution was transferred into the slurry of N-methyl-N-(2-[4-hydroxyphenyl]ethyl) amine at about 5° C. and then stirred for about 0.5 hours under an atmosphere of nitrogen. The solution was concentrated under vacuum and then cooled to between 25 to 35° C. To this was then added a 15% w/v solution of NaOH in methanol (0.173 Kg sodium hydroxide in methanol 0.910 Kg) and was then heated to between 25 to 35° C. The solution was stirred for about 8 hours and then the pH was adjusted to between 2 to 5 with 32% hydrochloric acid (˜0.6 Kg). The solution was concentrated and the residue was cooled to about 30° C. Dichloromethane (6.628 Kg) and water (15 Kg) were added into the above mixture and then cooled to about 5° C. and was then stirred for about 2 hours. The solidified product was filtered and washed twice with dichloromethane (0.663 Kg each) to provide crude N-methyl-N-(2-[4-hydroxyphenyl]ethyl)-2-bromo-5-hydroxy-4-methoxy benzene carboxamide (C2).

Workup

  1. concentrationThe solution was concentrated under vacuum
  2. additionTo this was then added a 15% w/v solution of NaOH in methanol (0.173 Kg sodium hydroxide in methanol 0.910 Kg)
  3. temperaturewas then heated to between 25 to 35° C
  4. stirringThe solution was stirred for about 8 hours
  5. concentrationThe solution was concentrated
  6. temperaturethe residue was cooled to about 30° C
  7. additionDichloromethane (6.628 Kg) and water (15 Kg) were added into the above mixture
  8. temperaturecooled to about 5° C.
  9. stirringwas then stirred for about 2 hours
  10. filtrationThe solidified product was filtered
  11. washwashed twice with dichloromethane (0.663 Kg each)

Sources & evidence

ORD record
ord-0064772b1bd74211ba0ff5f218a62651
Source dataset
uspto-grants-2011_07
Patent number
US07985879B2

Reaction notes

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