Lithium Hydroxide → HCID 21051840, compound

HRID 854735Notes

Reaction equation

HRID 854735 reaction equation
C[O:2][C:3](=[O:22])[CH:4]([C:11]1[CH:16]=[CH:15][C:14](F)=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:12]=1)[CH2:5][C@H:6]1[CH2:10][CH2:9][CH2:8][O:7]1.[CH3:23][S-:24].[Na+].[OH-].[Li+]>CN(C)C=O>[CH3:23][S:24][C:14]1[CH:15]=[CH:16][C:11]([CH:4]([CH2:5][C@H:6]2[CH2:10][CH2:9][CH2:8][O:7]2)[C:3]([OH:2])=[O:22])=[CH:12][C:13]=1[C:18]([F:21])([F:20])[F:19]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 4378561Sodium methanethiolateHCID 67482102HCID 67482102, compound

Product 1

HCID 21051840HCID 21051840, compoundYield 83.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(4-fluoro-3-trifluoromethyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (1.97 g, 6.15 mmol) in dry N,N-dimethylformamide (20 mL) at 25° C. under argon was carefully treated with sodium thiomethoxide (0.680 g, 9.27 mmol) and was then heated at 100° C, for 3 h. The reaction mixture was then concentrated in vacuo to remove N,N-dimethylformamide. The remaining residue was suspended in a saturated aqueous ammonium chloride solution (100 mL) and was extracted with ethyl acetate (2×200 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was then dissolved in methanol (40 mL) and was treated with a 0.8M aqueous lithium hydroxide solution (20.60 mL, 16.7 mmol). The reaction mixture was stirred at 25° C. for 16 h and then was concentrated in vacuo to remove methanol. The remaining aqueous layer was acidified to pH=2 with a 10% aqueous hydrochloric acid solution and then was extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford pure 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid (1.71 g, 83%) as a light yellow oil: [αC]23589=−23.26° (c=0.49, chloroform); EI-HRMS m/e calcd for C15H17F3O3S (M−H2O)+ 316.0744. found 316.0749.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customto remove N,N-dimethylformamide
  3. extractionwas extracted with ethyl acetate (2×200 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue was then dissolved in methanol (40 mL)
  8. concentrationwas concentrated in vacuo
  9. customto remove methanol
  10. extractionwas extracted with ethyl acetate (2×200 mL)
  11. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×100 mL)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-58419ecea6654a0db37cea23f0d73954
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

Loading…