Nitric Acid → 1-(Benzyloxy)-2,3-dimethoxybenzene

HRID 619366Notes

Reaction equation

HRID 619366 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N+]([O-])=O)[CH:12]=[C:11]([O:18][CH3:19])[C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1C=CC=C(OC)C=1OC)(=O)C1C=CC=CC=1.[N+]([O-])(O)=O>C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:18][CH3:19])[C:10]=1[O:20][CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 13270875(2,3-Dimethoxyphenyl)(phenyl)methanoneHCID 223268711-Benzyloxy-2,3-dimethoxy-5-nitrobenzene

Product 1

HCID 134470881-(Benzyloxy)-2,3-dimethoxybenzene

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

from 2-chloro-N-(3-methoxyphenyl)-4-pyrimidineamine (1 62 mg, 0.69 mmol) [see Example 92] and 3-benzyloxy-4,5-dimethoxyaniline (180 mg, 0.69 mmol) to afford the title compound (255 mg) as an off-white solid m.p. 83-84°. δH (CDCl3) 8.01 (1H, d, J 5.8 Hz), 7.45-7.22 (6H, m), 6.95 (3H, m), 6.90 (1H, d, J 7.6 Hz), 6.79 (1H, d, J 2.4 Hz), 6.68 (1H, d, J 7.6 Hz), 6.48 (1H, s), 6.17 (1H, d, J 5.8 Hz), 5.11 (2H, s), 3.86 (3H, s), 3.82 (3H, s) and 3.78 (3H, s). MS m/z 369 (M+H)+. The 3-benzyloxy-4,5-dimethoxyaniline was prepared by heating a solution of 1-benzyloxy-2,3-dimethoxy-5-nitrobenzene (1.80 g, 6.23 mmol) in ethanol (15 ml) with saturated aqueous sodium hydrosulphite (20 ml) at reflux for 2 h. An additional quantity of sodium hydrosulphite (20 ml) was added and reflux continued for a further 4 h. The reaction mixture was reduced to a small volume then diluted with water and extracted three times with ethyl acetate. The organic phase was dried (MgSO4) and evaporated to give the crude product which was recrystallised from etherhexane to give the desired product (356 mg) as a white crystalline solid m.p. 118-120°. MS m/z 260 (M+H)+. The 1-benzyloxy-2,3-dimethoxy-5-nitrobenzene used as starting material was prepared by treating a solution of 1-benzoyl-2,3-dimethoxybenzene (7.25 g, 29.66 mmol) in glacial acetic acid (15 ml) portionwise with 70% nitric acid (2.84 ml) at room temperature. After 2 h, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic phase was washed with 1 M NaOH, then brine, dried (MgSO4) and evaporated. The crude product was purified by column chromatography [silica 20% ethyl acetate-hexane] to give, after recrystallisation from CH2Cl2 -hexane, the desired product (1.89 g) as a white solid m.p. 101-102°. MS m/z (relative intensity) (M+H)+ 289 [(M+H),+ 2%] 91 [100%]. 1-Benzyloxy-2,3-dimethoxybenzene was prepared by the method of F Dietl et al Synthesis, 626 (1985).

Workup

  1. customwas recrystallised from etherhexane
  2. customto give the desired product (356 mg) as a white crystalline solid m.p. 118-120°
  3. customwas prepared
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with 1 M NaOH
  6. dry with materialbrine, dried (MgSO4)
  7. customevaporated
  8. customThe crude product was purified by column chromatography [silica 20% ethyl acetate-hexane]
  9. customto give
  10. customafter recrystallisation from CH2Cl2 -hexane

Sources & evidence

ORD record
ord-4ff5c1c989624de6a8b2aa5624d3a62a
Source dataset
uspto-grants-1999_09
Patent number
US05958935

Reaction notes

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