4-Methoxybenzoic Acid → HCID 58828528, compound

HRID 2358301Notes

Reaction equation

HRID 2358301 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1.CN(CCN(C)C)C.[Li]C(CC)C.[F:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[C:28](OC)=[O:29]>C1COCC1.C1(C)C=CC=CC=1>[F:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[C:28]([C:10]1[CH:11]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=1[C:7]([OH:9])=[O:8])=[O:29]

Participants

7

Reactant 4

HCID 74784-Methoxybenzoic AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 67854Benzoic acid, 2-fluoro-, methyl esterHCID 178418400CID 53628100

Product 1

HCID 58828528HCID 58828528, compoundYield 52.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(Methoxy)benzoic acid (5.00 g, 32.9 mmol) was azeotroped with toluene thrice, then dissolved in 80 mL of dry THF. TMEDA (10.9 mL, 72.3 mmol) was added, and the mixture was cooled to −78° C. sec-BuLi (51.6 mL of 1.40 M in cyclohexane, 72.3 mmol) was added dropwise over a period of 30 minutes, and the solution was stirred for 15 minutes. Methyl 2-fluorobenzoate (5.02 mL, 39.4 mmol) was added in 1 portion and, after stirring for 15 minutes, the reaction was quenched with 20 mL of water. The mixture was warmed to ambient temperature and poured into 1.5 L of water. 30 mL 1N NaOH was added and the aqueous layer was extracted 1× with EtOAc; after which the organic layer was discarded. The aqueous layer was acidified with conc. HCl until pH=1 and then extracted 2× with EtOAc. The combined organic extracts were dried with Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by flash chomatography through SiO2 (40-100% EtOAc/hexane) to provide the desired product (4.72 g, 52% yield) as a white solid. ESI+MS: 275.2 [M+H+].

Workup

  1. additionwas added dropwise over a period of 30 minutes
  2. stirringafter stirring for 15 minutes
  3. customthe reaction was quenched with 20 mL of water
  4. additionpoured into 1.5 L of water
  5. addition30 mL 1N NaOH was added
  6. extractionthe aqueous layer was extracted 1× with EtOAc
  7. extractionextracted 2× with EtOAc
  8. dry with materialThe combined organic extracts were dried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by flash chomatography through SiO2 (40-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-6b32850355c141a3a3aee924239bc8b4
Source dataset
uspto-grants-2010_07
Patent number
US07763614B2

Reaction notes

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