Carbon Dioxide → 2-Fluoro-3-methoxybenzoic acid

HRID 865286Notes

Reaction equation

HRID 865286 reaction equation
CC(C)([O-])C.[K+].C([Li])CCC.[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20].[C:21](=[O:23])=[O:22]>O.O1CCCC1>[F:12][C:13]1[C:14]([O:19][CH3:20])=[CH:15][CH:16]=[CH:17][C:18]=1[C:21]([OH:23])=[O:22]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 675762-FluoroanisoleHCID 23665647Potassium tert-butoxideHCID 178418339Butyllithium

Product 1

HCID 33906792-Fluoro-3-methoxybenzoic acidYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of potassium tert-butoxide (30.80 g, 274 mmol) and anhydrous tetrahydrofuran (300 mL) was cooled to -78° C. and treated with a 1.6M solution of n-butyllithium (172 mL, 275 mmol) in hexanes. After stirring for 15 minutes, 2-fluoroanisole (31.35 g, 248 mmol) was added and the reaction was stirred an additional 1.8 hours. The reaction was poured into a 2 L Erlenmeyer flask containing dry ice and warmed to room temperature. Water (250 mL) was added and after extracting with ether (160 mL), the aqueous layer was acidified with concentrated hydrochloric acid, and filtered to give 2-fluoro-3-methoxybenzoic acid (21.43 g, 51%) as a yellow solid: mp 155°-160° C.; 1H NMR (acetone-d6) 300 MHz 7.46 (ddd, J=6.0 Hz J=1.8 Hz J=1.4 Hz, 1H) 7.36 (dt, J=1.6 Hz J=8.1 Hz, 1H) 7.20 (dt, J=1.4 Hz J=8.1 Hz, 1H) 3.92 (s, 3H); 19F NMR (acetone-d6) 300 MHz -134.04 (m). Mass spectrum: M+H=171.

Workup

  1. stirringthe reaction was stirred an additional 1.8 hours
  2. additionThe reaction was poured into a 2 L Erlenmeyer flask
  3. temperaturewarmed to room temperature
  4. extractionafter extracting with ether (160 mL)
  5. filtrationfiltered

Sources & evidence

ORD record
ord-8f8a8a0ceb4c4f0db355cf12f1ea8c45
Source dataset
uspto-grants-1996_10
Patent number
US05565482

Reaction notes

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