Diethyl Ether → 4-Nitro-o-toluic acid

HRID 2251819Notes

Reaction equation

HRID 2251819 reaction equation
I[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:11].[C:12](=O)([O-:14])[O-:13].[K+].[K+].CN(C)C=O.C(OCC)C>O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd](Cl)Cl.CCCCCC>[N+:8]([C:7]1[CH:6]=[CH:5][C:4]([C:12]([OH:14])=[O:13])=[C:3]([CH3:11])[CH:2]=1)([O-:10])=[O:9]

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2347812-Iodo-3-nitrotoluene

Product 1

HCID 747904-Nitro-o-toluic acidYield 31.2%

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1.0 g(3.8 mmol) of 2-iodo-nitrotoluene, 2.1 g(15.2 mmol) potassium carbonate and 27 mg (0.038 mmol) of palladium(II) dichloride bis(triphenylphosphine) in a mixture of 5 mL of water and 10 mL, of N,N-dimethylformamide. This was placed in a Fisher/Porter bottle under 15 psig of carbon monoxideand heated at 70 C. for 16 hours. The solution became homogeneous when heated. The reaction was cooled, diethyl ether and water was added, the organic layer separated and discarded. The aqueous layer was acidified with 1N hydrochloric acid, extracted with ethyl acetate, washed with water, brine, dried over magnesium sulfate, filtered and concentrated to yield 0.5 g of crude material. This dissolved in ethyl acetate, hexane added and the resulting brown solid discarded. The filtrate was concentrated, and then recrystallized from diethyl ether/hexane to afford 215 mg of 4-nitro-2-methylbenzoic acid, m/e=182 (M+H). Part B. Preparation of Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-2-methyl-4-nitro

Workup

  1. temperatureheated at 70 C
  2. temperatureheated
  3. temperatureThe reaction was cooled
  4. customthe organic layer separated
  5. extractionextracted with ethyl acetate
  6. washwashed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield 0.5 g of crude material
  11. concentrationThe filtrate was concentrated
  12. customrecrystallized from diethyl ether/hexane

Sources & evidence

ORD record
ord-428877ef9f1140c891ccf3104469e283
Source dataset
uspto-grants-2008_01
Patent number
US07320983B2

Reaction notes

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