Sodium Hydroxide → (E)-2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylic acid

HRID 1350294Notes

Reaction equation

HRID 1350294 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](=[CH:17]\[CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)/[C:12]([O:14]CC)=[O:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[OH-].[Na+]>CO>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8](/[C:11](=[CH:17]\[CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)/[C:12]([OH:14])=[O:13])=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86594313(E)-ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylate

Product 1

HCID 58860809(E)-2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

LDA (24 mL of a 1.8M solution in n-C7H16-THF-PhEt, 43.3 mmol) was added dropwise to a stirred solution of DMPU (19 mL, 153.0 mmol) in anhydrous THF (100 mL) at −78° C. After 30 min, a solution of ethyl (4-methanesulfonylphenyl)-acetate (Preparation 15, 5.00 g, 20.6 mmol) in anhydrous THF (42 mL) was added dropwise. The mixture was stirred further for 1 h, before being treated dropwise with a solution of tetrahydropyran-4-carboxaldehyde (2.36 g, 20.6 mmol) in anhydrous THF (25 mL). After being allowed to warm up to 20° C. over 16 h, the reaction was quenched with saturated aqueous NH4Cl (210 mL). The THF was removed under reduced pressure, then the remainder was extracted with EtOAc (3×250 mL). The combined EtOAc extracts were dried (MgSO4), filtered, and concentrated. Column chromatography (IH-EtOAc, 7:3) furnished (E)-ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylate: m/z (ES+)=356.2 [M+NH4]+. A solution of this ester (6.46 g, 19.1 mmol) in MeOH (30 mL) and 1M NaOH (40 mL, 40.0 mmol) was heated under reflux for 1 h. On cooling, the mixture was washed with EtOAc. The aqueous phase was acidified with 1M HCl, before being extracted with EtOAc. The combined organic extracts were dried (MgSO4). Filtration and solvent evaporation afforded the title compound: m/z (ES+)=621.3 [2M+H]+.

Workup

  1. temperatureunder reflux for 1 h
  2. temperatureOn cooling
  3. washthe mixture was washed with EtOAc
  4. extractionbefore being extracted with EtOAc
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationFiltration and solvent evaporation

Sources & evidence

ORD record
ord-dff44d212f8748cd8348d455a3647049
Source dataset
uspto-grants-2007_05
Patent number
US07214681B2

Reaction notes

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