Ethyl phenylacetate → HCID 67357346, compound

HRID 1667184Notes

Reaction equation

HRID 1667184 reaction equation
C1([CH2:7][C:8]([O:10]CC)=[O:9])C=CC=CC=1.[CH3:13][C:14]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][NH:16][C:15]1=[O:20].CC(C)([O-])C.[K+].BrCC(OCC)=O.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:13][C:14]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][NH:16][C:15]1=[O:20].[CH3:13][C:14]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][N:16]([CH2:7][C:8]([OH:10])=[O:9])[C:15]1=[O:20]

Participants

9

Reactant 5

HCID 7590Ethyl phenylacetateHCID 7748Ethyl bromoacetateHCID 14798Sodium HydroxideHCID 23665647Potassium tert-butoxideHCID 67358232HCID 67358232, compound

Product 2

HCID 67357346HCID 67357346, compoundHCID 67358232HCID 67358232, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

3-Methyl-3-phenylpiperidin-2-one is prepared using the procedures described in Examples 91A and 91B substituting ethyl 2-phenylpropionate for ethyl 2-phenylacetate. To 3-methyl-3-phenylpiperidin-2-one (1.01 g, 5.34 mmol) in tetrahydrofuran (3 mL) was added potassium t-butoxide (1.0 Min tetrahydrofuran, 6.40 mL, 6.40 mmol), and the mixture was allowed to stir at room temperature for 30 minutes. To the mixture was added ethyl 2-bromoacetate (0.591 mL, 5.34 mmol). The reaction was heated to 60° C. and stirred for 2 hours. The reaction was cooled, diluted with ethyl acetate (50 mL), washed with 1 N HCl (25 mL) and brine (25 mL), dried over magnesium sulfate and concentrated. The residue was loaded directly onto a SF25-40 silica gel column (Analogix®, Burlington, Wis.), and the intermediate ethyl ester was eluted using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate over 30 minutes (flow=30 mL/minute). The ethyl ester was dissolved in ethanol (10 mL) and sodium hydroxide (2.0 M, 5.34 mL, 10.67 mmol) was added. After stirring for 30 minutes, thin layer chromatography (100% ethyl acetate) showed complete consumption of the starting material. The reaction was diluted with ethyl acetate (50 mL), washed with 1 N HCl (50 mL) and brine (50 mL), dried over magnesium sulfate, and concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.42-7.11 (m, 5H), 4.28 (d, J=16.7, 1H), 4.12 (d, J=16.7, 1H), 3.59-3.33 (m, 2H), 2.23 (dt, J=4.5, 13.5, 1H), 2.07-1.89 (m, 1H), 1.85-1.66 (m, 2H), 1.61 (s, 3H); MS (APCI+) m/z 248 (M+H)+.

Workup

  1. temperatureThe reaction was heated to 60° C.
  2. stirringstirred for 2 hours
  3. temperatureThe reaction was cooled
  4. washwashed with 1 N HCl (25 mL) and brine (25 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. washthe intermediate ethyl ester was eluted
  8. customover 30 minutes
  9. dissolutionThe ethyl ester was dissolved in ethanol (10 mL)
  10. stirringAfter stirring for 30 minutes
  11. customconsumption of the starting material
  12. additionThe reaction was diluted with ethyl acetate (50 mL)
  13. washwashed with 1 N HCl (50 mL) and brine (50 mL)
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-d3e725fca0ff49f787224e848f8dc3b7
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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