Triethyl phosphonoacetate → 3-Ethoxycarbonylmethylene-9-aza-bicyclo[3.3.1]nonane-9-carboxylic acid tert-butyl ester

HRID 1455552Notes

Reaction equation

HRID 1455552 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].[H-].[Na+].[C:17]([O:21][C:22]([N:24]1[CH:29]2[CH2:30][CH2:31][CH2:32][CH:25]1[CH2:26][C:27](=O)[CH2:28]2)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C1COCC1>[C:17]([O:21][C:22]([N:24]1[CH:25]2[CH2:32][CH2:31][CH2:30][CH:29]1[CH2:28][C:27](=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[O:14])[CH2:26]2)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 45790088N-Boc-9-azabicyclo[3.3.1]nonan-3-one

Product 1

HCID 684432003-Ethoxycarbonylmethylene-9-aza-bicyclo[3.3.1]nonane-9-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

0.54 ml of (diethoxy-phosphoryl)-acetic acid ethyl ester are added dropwise to a suspension of 108 mg of NaH (55% in mineral oil) in 5 ml of THF at 0°. The mixture obtained is stirred and 650 mg of 3-oxo-9-aza-bicyclo[3.3.1]nonane-9-carboxylic acid tert-butyl ester in 5 ml of THF are slowly added. The mixture obtained is stirred at 60° C. for 3 days, diluted with c-HEX and washed with 1M aqueous NaH2PO4 and saturated aqueous NaHCO3 solution. The organic layer obtained is dried, solvent is evaporated and the evaporation residue obtained is subjected to chromatography on silica gel. 3-Ethoxycarbonylmethylene-9-aza-bicyclo[3.3.1]nonane-9-carboxylic acid tert-butyl ester is obtained in the form of an oil. 13C-NMR: 171.79, 154.45, 154.27, 133.38, 132.77, 127.11, 126.30, 79.64, 79.54, 61.03, 61.00, 48.59, 47.20, 46.81, 45.22, 42.72, 33.61, 33.42, 32.59, 32.17, 30.73, 30.07, 28.87, 28.57, 28.13, 16.48, 14.59.

Workup

  1. customThe mixture obtained
  2. customThe mixture obtained
  3. stirringis stirred at 60° C. for 3 days
  4. additiondiluted with c-HEX and
  5. washwashed with 1M aqueous NaH2PO4 and saturated aqueous NaHCO3 solution
  6. customThe organic layer obtained
  7. customis dried
  8. customsolvent is evaporated
  9. customthe evaporation residue obtained

Sources & evidence

ORD record
ord-3f776ac227b247348c05611328957d6b
Source dataset
uspto-grants-2009_01
Patent number
US07482462B2

Reaction notes

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