2-Chloro-4-nitrobenzoic acid → 2-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-4-nitrobenzoic acid

HRID 1954418Notes

Reaction equation

HRID 1954418 reaction equation
Cl[C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C[O-].[Na+].[C:17]([O:24][CH3:25])(=[O:23])[CH2:18][C:19]([O:21][CH3:22])=[O:20]>[Cu]Br>[CH3:22][O:21][C:19](=[O:20])[CH:18]([C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])[C:17]([O:24][CH3:25])=[O:23]

Participants

5

Reactant 3

HCID 74482-Chloro-4-nitrobenzoic acidHCID 7943Dimethyl malonateHCID 10942334Sodium Methoxide

Product 1

HCID 105900782-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-4-nitrobenzoic acidYield 70%

Reagents, catalysts & solvents 1

HCID 24593copper(I) bromideCatalyst

Conditions

Temperature
70 °C

Procedure

A solution of 2-chloro-4-nitrobenzoic acid (75 g, 372 mmol) in dimethyl malonate (900 mL) was perfused with nitrogen for 15 min. Sodium methoxide (48.3 g, 894 mmol) was added in one portion and the contents exothermed to 48° C. Fifteen minutes later, copper (I) bromide (5.4 g, 37 mmol) was added in one portion and the contents were heated to 70° C. for 24 hrs. The reaction, which was 70% complete as determined by NMR, was subsequently heated to 85° C. for 5 hrs to completely consume the remaining 2-chloro4-nitrobenzoic acid. Water (900 mL) was added to the cooled reaction followed by hexanes (900 mL). The aqueous layer was separated, toluene (900 mL) was added, the mixture was filtered and aqueous layer separated. Fresh toluene (1800 mL) was added to the aqueous layer and the biphasic mixture acidified with 6N aqueous HCl (90 mL). A white precipitate formed and the contents were stirred for 18 hrs. The product was filtered off and dried to give a white solid (78.1 g, 70%) mp 153° C.

Workup

  1. customexothermed to 48° C
  2. customThe reaction, which
  3. temperaturewas subsequently heated to 85° C. for 5 hrs
  4. customto completely consume the remaining 2-chloro4-nitrobenzoic acid
  5. additionWater (900 mL) was added to the cooled reaction
  6. customThe aqueous layer was separated
  7. additiontoluene (900 mL) was added
  8. filtrationthe mixture was filtered
  9. customaqueous layer separated
  10. additionFresh toluene (1800 mL) was added to the aqueous layer
  11. customA white precipitate formed
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-e3b494decc724c88a8a9efe3d2ade374
Source dataset
uspto-grants-2000_09
Patent number
US06121283

Reaction notes

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