Ethyl orthoformate → 7-Methoxybenzo[d]oxazole

HRID 1643360Notes

Reaction equation

HRID 1643360 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-cd1c342188234e98bba26d48d6a8cc54
Source dataset
uspto-grants-2012_02
Patent number
US08119631B2

Reaction notes

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