Water → tert-Butyl diethylphosphonoacetate

HRID 1789789Notes

Reaction equation

HRID 1789789 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[H-].[Na+].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32]Br)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].O>CN(C=O)C>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32][CH:9]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21].[CH2:7]([O:6][P:4]([CH2:9][C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2773685tert-Butyl diethylphosphonoacetateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate

Product 2

HCID 2773685tert-Butyl diethylphosphonoacetateHCID 54388803HCID 54388803, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-Butyl diethylphosphonoacetate (75.0 g, 297.32 mmol) was added dropwise to a suspension of sodium hydride (8.03 g, 334.58 mmol) in DMF (450 mL) at 0° C. under nitrogen. The mixture was stirred at 0° C. for 0.5 h and at room temperature for 0.5 h. 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester (20.68 g, 74.34 mmol) in DMF (50 mL) was added dropwise to the reaction mixture and the reaction was heated to 60° C. and stirred for 16 h. The reaction was cooled to room temperature, poured into H2O and extracted with ethyl acetate. The organic layers were combined and washed with water. The organic layer was dried, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (ethyl acetate/hexane, 3:7) to give 4-[2-tert-Butoxycarbonyl -2-(diethoxy-phosphoryl)-ethyl]-piperidine-1-carboxylic acid tert-butyl ester and unreacted t-butyl diethylphosphonoacetate. The product was 47% pure by HPLC. The product was further purified by vacuum distillation to give 77% purity. This mixture was taken on to the next reaction.

Workup

  1. temperaturethe reaction was heated to 60° C.
  2. stirringstirred for 16 h
  3. temperatureThe reaction was cooled to room temperature
  4. extractionextracted with ethyl acetate
  5. washwashed with water
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography (ethyl acetate/hexane, 3:7)

Sources & evidence

ORD record
ord-3766d5d750f448b4a39ea86404d088d3
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

Loading…