Carbon Dioxide → 3-{4-[(3-Fluorophenyl)methoxy]phenyl}prop-2-ynoic acid

HRID 2184354Notes

Reaction equation

HRID 2184354 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[CH:14])=[CH:9][CH:8]=1.C([Li])CCC.[C:23](=[O:25])=[O:24].Cl>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:23]([OH:25])=[O:24])=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 224766251-[(4-Ethynylphenoxy)methyl]-3-fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 692917433-{4-[(3-Fluorophenyl)methoxy]phenyl}prop-2-ynoic acidYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

1.93 g (8.5 mmol) of 1-(3-fluoro-benzyloxy)-4-ethynyl-benzene is dissolved in 30 ml THF and cooled to −78° C. 5.8 ml (9.4 mmol) of a 1.6 molar solution of n-butyl lithium is slowly added under stirring. The resulting solution is stirred at −78° C. for 30 minutes. An excess of solid carbon dioxide is added and the suspension is slowly allowed to warm to RT. Water is added and the mixture is acidified by addition of aqueous 0.1 molar hydrochloric acid. Extraction with ethyl acetate yields a semi-solid residue which is triturated in diethyl ether to give 1.58 g (68%) of a colorless solid. MS (neg.ions): m/e=269.1 (M−H).

Workup

  1. stirringThe resulting solution is stirred at −78° C. for 30 minutes
  2. temperatureto warm to RT
  3. extractionExtraction with ethyl acetate
  4. customyields a semi-solid residue which
  5. customis triturated in diethyl ether

Sources & evidence

ORD record
ord-5e595702ed7b4b95a6f0abd523e25241
Source dataset
uspto-grants-2005_05
Patent number
US06900354B2

Reaction notes

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