Dimethylformamide → HCID 67311651, compound

HRID 1930302Notes

Reaction equation

HRID 1930302 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4](O)=O.CN(C)[CH:16]=[O:17].[C:19](Cl)(=[O:23])[C:20](Cl)=O.[Si](C=[N+]=[N-])(C)(C)C>C(Cl)Cl>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[CH2:4][C:16]([O:23][CH2:19][C:20]1[CH:9]=[CH:10][CH:2]=[CH:3][CH:4]=1)=[O:17]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 167693TrimethylsilyldiazomethaneHCID 5196832-Methyl-5-nitrobenzoic acid

Product 1

HCID 67311651HCID 67311651, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

In methylene chloride (50 mL) was placed 2-methyl-5-nitrobenzoic acid (3.00 g, 16.6 mmol) and 1 microdrop of dimethylformamide. The solution was cooled to 0° C. and to this was added oxalyl chloride (3.15 g, 24.8 mmol). After 15 minutes the mixture was allowed to warm to RT and stirred a further 2 hours. The mixture evaporated at reduced pressure. This residue was dissolved in THF (60 mL) and cooled to 0° C. To this was added the 2.00N TMS-diazomethane (18.6 mL, 37.3 mmol) and the mixture stirred at 0° C. for 5 hrs. The solution was evaporated at reduced pressure and the new residue was treated with benzyl alcohol (15 mL) and 2,4,6-collidine (10 mL) and warmed to 180° C. for 15 min. After cooling to RT and diluting with ethyl acetate (100 mL), the resulting solution was washed successively with water (2×100 mL), 5% citric acid (100 mL, till pH of aqueous phase is acidic), water (100 mL) and brine (100 mL). The solvent was removed at reduced pressure and the resultant oil was dried on the high vacuum line at 65° C. to remove most excess benzyl alcohol. The oil was purified by chromatography (Biotage Si-40 column, 10-40% ethyl acetate/Hex—1398 mL) to give benzyl 2-(2-methyl-5-nitrophenyl)acetate as an oil (2.465 g, 52% yield) which was used as is.

Workup

  1. temperatureto warm to RT
  2. customThe mixture evaporated at reduced pressure
  3. dissolutionThis residue was dissolved in THF (60 mL)
  4. temperaturecooled to 0° C
  5. stirringthe mixture stirred at 0° C. for 5 hrs
  6. customThe solution was evaporated at reduced pressure
  7. additionthe new residue was treated with benzyl alcohol (15 mL) and 2,4,6-collidine (10 mL)
  8. temperaturewarmed to 180° C. for 15 min
  9. temperatureAfter cooling to RT
  10. additiondiluting with ethyl acetate (100 mL)
  11. washthe resulting solution was washed successively with water (2×100 mL), 5% citric acid (100 mL
  12. customThe solvent was removed at reduced pressure
  13. customthe resultant oil was dried on the high vacuum line at 65° C.
  14. customto remove most excess benzyl alcohol
  15. customThe oil was purified by chromatography (Biotage Si-40 column, 10-40% ethyl acetate/Hex—1398 mL)

Sources & evidence

ORD record
ord-b27d6fc257134550bd677e116c7620f8
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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