Acetic Acid → Benzyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate

HRID 1697848Notes

Reaction equation

HRID 1697848 reaction equation
[CH2:1]([O:8][C:9]1[CH:24]=[CH:23][C:12]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])=[CH:11][C:10]=1[O:25][CH3:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.S(=O)(=O)(O)O.[N+:36]([O-])([OH:38])=[O:37]>ClCCl>[CH2:1]([O:8][C:9]1[C:10]([O:25][CH3:26])=[CH:11][C:12]([C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:14])=[C:23]([N+:36]([O-:38])=[O:37])[CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 22070405Benzyl 4-(benzyloxy)-3-methoxybenzoate

Product 1

HCID 10894498Benzyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

Benzyl 4-(benzyloxy)-3-methoxybenzoate (135 g) was dissolved in dichloromethane (339 ml). Glacial acetic acid (175.5 g) was added and the mixture cooled to 110° C. Concentrated sulfuric acid (151.6 g) was added in a controlled manner maintaining the temperature of the reaction mixture below 25° C. Concentrated nitric acid (61.6 g) was then added in 15 minutes keeping the temperature of the reaction mixture below 25° C. The reaction mixture was then heated to 40° C. and stirred for 3 hours. The lower aqueous layer was removed and the organic layer was washed twice with water (2×168 ml). The organic layer was distilled to at atmospheric pressure to remove dichloromethane (186 ml). Isopropanol (339 ml) was added to the reaction mixture at 40° C. The reaction mixture was held at 40° C. for 15 minutes. The resulting suspension was then cooled to 20° C. within 30 minutes, then to 5° C. and held at this temperature for one hour. The product (benzyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate) was isolated by filtration, washed with isopropanol (336 ml) and dried at less than 25° C. Yield: 135.7 g, 89.6%; NMR Spectrum (CDCl3) 3.9 (s, 3H), 5.2 (s, 2H), 5.3 (s, 2H), 7.1 (s, 1H), 7.3-7.4 (m, 100H), 7.5 (s, 1H); Mass Spectrum (M+H)+=394.1.

Workup

  1. temperaturemaintaining the temperature of the reaction mixture below 25° C
  2. customthe temperature of the reaction mixture below 25° C
  3. temperatureThe reaction mixture was then heated to 40° C.
  4. customThe lower aqueous layer was removed
  5. washthe organic layer was washed twice with water (2×168 ml)
  6. distillationThe organic layer was distilled to at atmospheric pressure
  7. customto remove dichloromethane (186 ml)
  8. additionIsopropanol (339 ml) was added to the reaction mixture at 40° C
  9. waitThe reaction mixture was held at 40° C. for 15 minutes
  10. temperatureThe resulting suspension was then cooled to 20° C. within 30 minutes
  11. waitto 5° C. and held at this temperature for one hour

Sources & evidence

ORD record
ord-60e2a4a99e7b4a62a9e529c55adfc56e
Source dataset
uspto-grants-2012_04
Patent number
US08163926B2

Reaction notes

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