ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate → 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetic acid

HRID 890880Notes

Reaction equation

HRID 890880 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1)[O:5][CH2:6][C:7]([O:9]CC)=[O:8]>[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1)[O:5][CH2:6][C:7]([OH:9])=[O:8]

Participants

4

Reactant 1

HCID 22246123ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate

Product 1

HCID 222462103-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetic acidYield 95%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 3939Lithium HydroxideSolvent

Procedure

A solution of ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate (Step 1) (0.3 g, 1 mmol) in ethanolic LiOH (1M, 1.5 mL) was stirred at room temperature for 2 h. The reaction mixture was diluted with 5% citric acid (10 mL) and extracted with ether (2×15 mL). The ether extracts were combined and washed with water (2×20 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to give 0.26 g (95%) of 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetic acid as a colorless viscous liquid: 1H NMR (CDCl3/300 MHz) δ 6.78 (d, 2H, J=10.5 Hz), 6.50 (d, 1H, J=10.5 Hz), 4.68 (s, 2H), 3.82 (m, 4H), 2.99 (s, 3H), 1.92 (m, 4H); FABMS m/z=284 (M+H). HRMS calcd for C14H17FO5 283.0982, found 283.0993.

Workup

  1. extractionextracted with ether (2×15 mL)
  2. washwashed with water (2×20 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6262ba12f0734e0c95005c779cfd2498
Source dataset
uspto-grants-2006_02
Patent number
US06998415B2

Reaction notes

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