Cesium fluoride → 1,1-Dimethylethyl 4-(4-fluorophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 270021Notes

Reaction equation

HRID 270021 reaction equation
FC(F)(F)C(O[C:6]1[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH:11]=1)=O.[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.[F-].[Cs+]>COCCOC.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:6]2[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:10][CH:11]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 2856454-Fluorophenylboronic acidHCID 22179822tert-butyl 4-[(trifluoroacetyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 157514261,1-Dimethylethyl 4-(4-fluorophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylateYield 78.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of Example 6A (4.0 g, 12 mmol) and 4-fluorophenylboronic acid (1.68 g, 12 mmol) in 1,2-dimethoxyethane (100 mL) and methanol (50 mL) was treated with tetrakis(triphenylphosphine)palladium(0) (0.416 g, 0.36 mmol) and CsF (3.64 g, 24 mmol), heated to reflux, and stirred overnight. The reaction was concentrated and the concentrate was dissolved in ethyl acetate (100 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 1:6 ethyl acetate/hexanes to provide the desired product (2.6 g, 78%). MS (CI) m/e 278 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. concentrationThe reaction was concentrated
  4. dissolutionthe concentrate was dissolved in ethyl acetate (100 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  6. washthe combined extracts were washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe concentrate was purified by flash column chromatography on silica gel with 1:6 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-571d86a57ea44405b88ff06b0afe8ece
Source dataset
uspto-grants-2008_11
Patent number
US07449485B2

Reaction notes

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