Triethyl phosphonoacetate → Tert-butyl-3-(2-ethoxy-2-oxoethylidene)pyrrolidine-1-carboxylate

HRID 1253522Notes

Reaction equation

HRID 1253522 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[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19]1>O1CCCC1>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][C:18](=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:19]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylate

Product 1

HCID 67205087Tert-butyl-3-(2-ethoxy-2-oxoethylidene)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A flask was charged with NaH (50 g, 1.25 mol, 60% in mineral oil) and tetrahydrofuran (2,500 ml) and cooled to 0° C. A solution of ethyl 2-(diethoxyphosphoryl)acetate (260 g, 1.16 mol) in tetrahydrofuran F (200 ml) was added dropwise. The resulting solution was allowed stir for 1 h at 0° C. Then a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (215 g, 1.16 mol) in tetrahydrofuran (300 ml) was added dropwise. The resulting solution was allowed to stir for 0.5 hours at 0° C. The reaction mixture was quenched by the addition of 1,000 ml of saturated aqueous ammonium chloride. The resulting mixture was extracted with ethyl acetate (3×2,000 ml) and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/petroleum ether gradient) to afford tert-butyl-3-(2-ethoxy-2-oxoethylidene)pyrrolidine-1-carboxylate as colorless oil.

Workup

  1. stirringto stir for 0.5 hours at 0° C
  2. customThe reaction mixture was quenched by the addition of 1,000 ml of saturated aqueous ammonium chloride
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×2,000 ml)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate/petroleum ether gradient)

Sources & evidence

ORD record
ord-bc171cbc8b694a03b158b31cd06dcfe9
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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