Sodium hydride → HCID 21959039, compound

HRID 854750Notes

Reaction equation

HRID 854750 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[C:9]([OH:11])=[O:10])=[CH:4][C:3]=1[C:19]([F:22])([F:21])[F:20].[H-].[Na+].[CH3:25][S-:26].[Na+]>CN(C)C=O>[CH3:25][S:26][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[C:9]([OH:11])=[O:10])=[CH:4][C:3]=1[C:19]([F:22])([F:21])[F:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4378561Sodium methanethiolateHCID 21958996HCID 21958996, compound

Product 1

HCID 21959039HCID 21959039, compoundYield 100.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(4-fluoro-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (5.20 g, 16.24 mmol) in dry N,N-dimethylformamide (90 mL) at 25° C. under argon was carefully treated with 95% sodium hydride (410 mg, 17.05 mmol). The reaction mixture was stirred at 25° C. for 30 min and then was treated with sodium thiomethoxide (2.40 g, 32.48 mmol). This mixture was heated at 100° C. for 4.5 h and then concentrated in vacuo to remove N,N-dimethylformamide. The residue was diluted with water (100 mL) and then was acidified to pH=2 using a 1N aqueous hydrochloric acid solution. The resulting aqueous layer was extracted with ethyl acetate (2×600 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98/2 chloroform/methanol to 9/1 chloroform/methanol) afforded 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (5.70 g, 100%) as a yellow gum: EI-HRMS m/e calcd for C16H19F3O3S (M+Na)+ 371.0899. found 371.0902.

Workup

  1. temperatureThis mixture was heated at 100° C. for 4.5 h
  2. concentrationconcentrated in vacuo
  3. customto remove N,N-dimethylformamide
  4. additionThe residue was diluted with water (100 mL)
  5. extractionThe resulting aqueous layer was extracted with ethyl acetate (2×600 mL)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2e37a5aba88f420ba93d297e95beea0e
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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