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

HRID 2056112Notes

Reaction equation

HRID 2056112 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[OH:9].[Br:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]=[C:18]=S)=[CH:13][CH:12]=1.C(N(CC)CC)C>O1CCCC1.S([O-])([O-])(=O)=O.[Cu+2]>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2[O:9][C:3]3[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=3[N:1]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 72642-Amino-4-methylphenolHCID 8471TriethylamineHCID 161334-Bromophenyl isothiocyanate

Product 1

HCID 21985825N-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amineYield 81.2%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-methylphenol (1.15 g, 9.34 mmol) was added to a solution of 4-bromophenyl isothiocyanate (2.00 g, 9.34 mmol) in tetrahydrofuran (35 mL) and the reaction was stirred at room temperature for 16 h. Anhydrous copper (II) sulfate (14.06 g, 88.10 mmol), silica gel (14.06 g), and triethylamine (1.3 mL, 9.34 mmol) were added, and the mixture was stirred at room temperature for 24 h. The reaction was concentrated under reduced pressure and then added to a silica pad and purified using 1:5 ethyl acetate:heptane (2 L) followed by diethyl ether as the eluent to afford N2-(4-bromophenyl)-5-methyl-1,3-benzoxazol-2-amine as a light brown solid (2.30 g, 81%); RP-HPLC Rt 16.437 min, 94% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); 1H NMR (400 MHz, d6-DMSO) 2.37 (3H, s), 6.94 (1H, d, J=8.1 Hz), 7.27 (1H, s), 7.36 (1H, d, J=8.1 Hz), 7.54 (2H, d, J=8.4 Hz), 7.72 (2H, d, J=8.4 Hz), and 10.72 (1H, s).

Workup

  1. stirringthe mixture was stirred at room temperature for 24 h
  2. concentrationThe reaction was concentrated under reduced pressure
  3. additionadded to a silica pad
  4. custompurified

Sources & evidence

ORD record
ord-dbe698aafe814655a509e4f8134b305c
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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