2-Amino-4-methylphenol → N-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amine

HRID 9588

Reaction equation

HRID 9588 reaction equation
BrC1C=CC(N=C=S)=CC=1.NC1C=C(C)C=CC=1O.[Br:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][C:31]2[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=2[OH:38])=S)=[CH:23][CH:22]=1.Cl.CN(C)CCCN=C=NCC>C(O)C.CCOCC>[Br:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28]2[O:38][C:32]3[CH:33]=[CH:34][C:35]([CH3:37])=[CH:36][C:31]=3[N:30]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 72642-Amino-4-methylphenolHCID 161334-Bromophenyl isothiocyanateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21985832N-(4-bromophenyl)-N'-(2-hydroxy-5-methylphenyl)thiourea

Product 1

HCID 21985825N-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amineYield 60%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

In a 250-mL round-bottom flask, 1-bromo-4-isothiocyanatobenzene (4.28 g, 20 mmol) and 2-amino-4-methyl-phenol (2.46 g, 20 mmol) were stirred in 120 mL ethanol at rt overnight. The formation of N-(4-bromophenyl)-N′-(2-hydroxy-5-methylphenyl)thiourea was confirmed by LC-MS. To the mixture, 1.5 eq. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) was added, and the reaction was stirred at rt for another 2 h. The reaction mixture was then heated at reflux for 6 h. The mixture was cooled to rt and the solvent was removed under reduced pressure. The solid was dissolved in EtOAc and washed with 2 N aqueous HCl and H2O. The organic layer was dried (MgSO4) and the solvent was removed under reduced pressure. The solid obtained was ultrasonicated in 30 mL ether and filtered to give the desired compound (3.64 g, 60%). 1H NMR (400 MHz, DMSO-d6) δ 10.70 (s, 1 H), 7.70 (m, 2 H), 7.55 (m, 2 H), 7.35 (d, 1 H), 7.25 (s, 1 H), 6.95 (d, 1 H), 2.40 (s, 3 H). LC-MS m/z 303.3 (MH+), ret. time 3.46 min.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 6 h
  3. temperatureThe mixture was cooled to rt
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe solid was dissolved in EtOAc
  6. washwashed with 2 N aqueous HCl and H2O
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customthe solvent was removed under reduced pressure
  9. customThe solid obtained
  10. filtrationfiltered

Sources & evidence

ORD record
ord-b422eaaf261343ee8c69e17472724450
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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