tert-Butanol → tert-Butyl 3-methyl-2-nitrobenzoate

HRID 1437856Notes

Reaction equation

HRID 1437856 reaction equation
[N+:1]([C:4]1[C:12]([CH3:13])=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])([O-:3])=[O:2].C1(S(Cl)(=O)=O)C=CC=CC=1.[C:24](O)([CH3:27])([CH3:26])[CH3:25]>N1C=CC=CC=1>[C:24]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][CH:11]=[C:12]([CH3:13])[C:4]=1[N+:1]([O-:3])=[O:2])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 7369Benzenesulfonyl chlorideHCID 215753-Methyl-2-nitrobenzoic acid

Product 1

HCID 57944066tert-Butyl 3-methyl-2-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

200 mg (1.104 mmol) of 2-nitro-3-methyl benzoic acid was dissolved in 16 ml of pyridine. 468 mg (2.208 mmol) of benzene sulfonyl chloride was added thereto and stirred at room temperature for 2 hours. 329 mg (4.146 mmol) of t-butanol was added thereto and stirred at room temperature for 15 hours. The reaction mixture was extracted with dichloromethane and pyridine was removed by using 2N hydrochloric acid. The organic layer was then neutralized with sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The resulting mixture was concentrated under reduced pressure. The concentrated product was then purified by the column chromatography (ethylacetate:hexane=1:30) to obtain 2-nitro-3-methyl benzoic acid t-butyl ester (Intermediate compound 43, 194 mg, Yield of the first step: 74%). 190 mg (0.800 mmol) of the first intermediate compound 43 as a starting material was subjected to the third step in the reaction of Example 1 to obtain 3-bromomethyl-2-nitrobenzoic acid t-butyl ester (Intermediate compound 44, 160 mg, Yield of the second step: 63%). 154 mg (0.487 mmol) of the intermediate compound 44 was dissolved in 7 ml of dichloromethane, and trifluoroacetic acid was added thereto. The mixture was stirred for 6 hours. When the reaction was completed, the resulting mixture was concentrated under reduced pressure and 3-bromomethyl-2-nitrobenzoic acid (Intermediate compound 45, 121 mg, Yield of the third step: 96%) was obtained. The intermediate compound 45 as a starting material was subjected to the fourth through sixth steps in the reaction of Example 3 to obtain the title compound 14 (83 mg, Yield of the sixth step: 14%).

Workup

  1. stirringstirred at room temperature for 15 hours
  2. extractionThe reaction mixture was extracted with dichloromethane and pyridine
  3. customwas removed
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationThe resulting mixture was concentrated under reduced pressure
  6. customThe concentrated product was then purified by the column chromatography (ethylacetate:hexane=1:30)

Sources & evidence

ORD record
ord-cc5850c6a9b948978fddab15c8d36435
Source dataset
uspto-grants-2009_11
Patent number
US07622612B2

Reaction notes

Loading…