Hydrochloric Acid → Diethyl (2,5-difluoro-4-nitrophenyl)propanedioate

HRID 1879109Notes

Reaction equation

HRID 1879109 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([F:13])=[CH:6][C:5]=1F.Cl[CH:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:17]([O:19][CH2:20][CH3:21])=[O:18].Cl>CN(C=O)C>[F:3][C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([F:13])=[CH:6][C:5]=1[CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 750121,2,4-Trifluoro-5-nitrobenzeneHCID 84182Diethyl chloromalonate

Product 1

HCID 59163358Diethyl (2,5-difluoro-4-nitrophenyl)propanedioateYield 54.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Crushed sodium hydroxide pellets (2.26 g, 56.5 mmol) were added portionwise over 20 minutes to solution of 1,2,4-trifluoro-5-nitrobenzene (5.0 g, 28.2 mmol) and diethyl chloropropanedioate (4.57 ml, 56.5 mmol) in dry DMF (50 ml) at 0° C. under argon. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was cooled to OC and acidified with 2N Hydrochloric acid (50 ml) then extracted with ethyl acetate (150 ml) and washed with water (150 ml). The organic layer was dried over magnesium sulphate, filtered and evaporated to an orange oil. Purified by chromatography on silica gel (Biotage SP4, 100 g silica column) eluting with 0-20% ethyl acetate/hexane to give the title compound as a yellow oil (4.84 g, 15.3 mmol). LC/MS: Rt=3.07, [MH]− 316.

Workup

  1. temperatureThe reaction mixture was cooled to OC
  2. extractionthen extracted with ethyl acetate (150 ml)
  3. washwashed with water (150 ml)
  4. dry with materialThe organic layer was dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated to an orange oil
  7. customPurified by chromatography on silica gel (Biotage SP4, 100 g silica column)
  8. washeluting with 0-20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-0e8ed66bc3f34fb5a750512e03d3b118
Source dataset
uspto-grants-2012_11
Patent number
US08314147B2

Reaction notes

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