Triethyl phosphonoacetate → tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

HRID 1501751Notes

Reaction equation

HRID 1501751 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.O=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1>O1CCCC1>[CH2:15]([O:14][C:12](=[O:13])[CH:11]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)[CH3:16]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 10333298tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 10-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a suspension of NaH (74.0 g, 2.16 mol 1.05 equiv, 70%) in tetrahydrofuran (2000 mL) at 0° C., then ethyl 2-(diethoxyphosphoryl)acetate (514 g, 2.06 mol, 1.05 equiv, 98%) was added dropwise with stirring at 0° C. This was followed by the addition of a solution of tert-butyl 4-oxopiperidine-1-carboxylate (400 g, 1.97 mol, 1.00 equiv, 98%) in tetrahydrofuran (1200 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 60 min at room temperature, then quenched by the addition of 2000 mL of water. The resulting solution was extracted with 2×1000 mL of ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was washed with 1×1000 mL of hexane and dried to afford tert-butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate.

Workup

  1. customInto a 10-L 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringwith stirring at 0° C
  4. stirringThe resulting solution was stirred for 60 min at room temperature
  5. customquenched by the addition of 2000 mL of water
  6. extractionThe resulting solution was extracted with 2×1000 mL of ethyl acetate
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. washThe residue was washed with 1×1000 mL of hexane
  10. customdried

Sources & evidence

ORD record
ord-da8ad3617d2b4b90916e24984009b2ac
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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