Carbon Dioxide → 3-Ethoxy-2-fluorobenzoic acid

HRID 1908135Notes

Reaction equation

HRID 1908135 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10])[CH3:2].C([Li])CCC.CN(C)CCN(C)CCN(C)C.[C:28](=[O:30])=[O:29]>C1COCC1.Cl>[CH2:1]([O:3][C:4]1[C:5]([F:10])=[C:6]([CH:7]=[CH:8][CH:9]=1)[C:28]([OH:30])=[O:29])[CH3:2]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 18196PentamethyldiethylenetriamineHCID 136291o-FluorophenatoleHCID 178418339Butyllithium

Product 1

HCID 467388193-Ethoxy-2-fluorobenzoic acidYield 65%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To 1-ethoxy-2-fluoro-benzene (1.0 g, 7.1 mmol) in THF (10 mL) at −78° C. was added dropwise butyllithium (4.5 mL of 1.6 M, 7.2 mmol) followed by N′-(2-dimethylaminoethyl)-N,N,N′-trimethyl-ethane-1,2-diamine (1.2 g, 7.2 mmol). The mixture was stirred for 3 h at −78° C. before it was transferred quickly via large cannula to a mixture of crushed dry ice (freshly crushed under N2) under ether. The mixture was warmed to RT, diluted with 30 mL of 2M HCl (aq.), extracted with ethyl acetate (2×30 mL), washed with 10 mL brine, and dried over MgSO4 to give 3-ethoxy-2-fluorobenzoic acid (65%) as a white solid. ESI-MS m/z calc. 184.1. found 185.1 (M+1)+; Retention time: 1.04 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.42-7.30 (m, 2H), 7.20-7.16 (m, 1H), 4.12 (q, J=7.0 Hz, 2H), 1.35 (t, J=7.0 Hz, 3H).

Workup

  1. customfreshly crushed under N2) under ether
  2. temperatureThe mixture was warmed to RT
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. washwashed with 10 mL brine
  5. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-5171aed74b4048aa8dedf088450cf13f
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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