Ethyl orthoformate → 7-Methoxybenzo[d]oxazole

HRID 613697

Reaction equation

HRID 613697 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH3:11])[C:5]=1[OH:12])([O-])=O.[CH2:13](OC(OCC)OCC)C>[Pd].C(O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:11][O:10][C:6]1[C:5]2[O:12][CH:13]=[N:1][C:4]=2[CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 2

HCID 31214Ethyl orthoformate2×HCID 109428552-Methoxy-6-nitrophenol

Product 1

HCID 184656867-Methoxybenzo[d]oxazoleYield 85.2%

Reagents, catalysts & solvents 3

HCID 6101p-Toluenesulfonic acidCatalyst2×HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of 2-nitro-6-methoxyphenol (2.62 g, 15.5 mmol) (EP 333176) and 10% Palladium on carbon (130 mg) in ethanol (50.0 ml) was stirred under an atmosphere of H2 for 75 min. The mixture was filtered through Celite® then immediately treated with p-toluenesulphonic acid (32.0 mg) and triethylorthoformate (6.45 ml, 38.8 mmol) then heated under reflux under an atmosphere of N2. After 20 h p-toluenesulphonic acid (30.0 mg) and triethylorthoformate (6.45 ml, 38.8 mmol) were added. After a total of 44 h heating, the reaction was allowed to cool and reduced in vacuo. The resulting residue was purified by flash chromatography (25:75 ethyl acetate/hexane) to give 1.97 g (85%) of the title compound as a yellow solid: m.p. 28-31° C.; IR (film) 1629, 1497, 1434, 1285, 1097; 1H NMR (CDCl3) δ 8.09 (1H, s), 7.40 (1H, d, J=8.0), 7.28 (1H, t, J=8.0), 6.89 (1H, d, J=8.0), 4.02 (3H, s); 13C NMR (CDCl3) δ 152.84, 145.82, 142.50, 139.99, 125.75, 113.42, 108.80, 56.97. Anal. Calcd. for C8H7N1O2. 0.1H2O: C, 63.65; H, 4.81; N, 9.29. Found: C, 63.43, H, 4.88, N, 9.05. M.S. (+FAB); 150 (M+ +1).

Workup

  1. filtrationThe mixture was filtered through Celite®
  2. temperaturethen heated
  3. temperatureunder reflux under an atmosphere of N2
  4. temperatureAfter a total of 44 h heating
  5. temperatureto cool
  6. customThe resulting residue was purified by flash chromatography (25:75 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-15a57cd0e1f04be896f19ccc5c1c02ec
Source dataset
uspto-grants-1999_12
Patent number
US06008217

Linked notes

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