Triethyl phosphonoacetate → HCID 117697698, compound

HRID 1778539Notes

Reaction equation

HRID 1778539 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:16])[CH2:7]P(OCC)(OCC)=O)[CH3:4].O=[C:18]1[CH2:25][CH:24]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:20]([CH2:21][O:22][CH2:23]2)[CH2:19]1>C1COCC1>[CH2:3]([O:5][C:6](=[O:16])[CH:7]=[C:18]1[CH2:19][CH:20]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]([CH2:23][O:22][CH2:21]2)[CH2:25]1)[CH3:4].[CH2:3]([O:5][C:6](=[O:16])[CH2:7][C:18]1[CH2:19][CH:20]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]([CH2:23][O:22][CH2:21]2)[CH:25]=1)[CH3:4]

Participants

6

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 185070529-Boc-7-oxa-9-azabicyclo[3.3.1]nonan-3-one

Product 2

HCID 117697563HCID 117697563, compoundYield 30.8%HCID 117697698HCID 117697698, compoundYield 46.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (396 mg, 60% dispersion in mineral oil, 9.9 mmol) in dry THF (5 ml) was added 2-diethoxyphosphorylacetic acid ethyl ester (2.40 g, 10.8 mmol) at 0° C. The resulting mixture was stirred at room temperature for 10 mins, and then heated at 80° C. for 20 mins. The reaction mixture was cooled down to room temperature. To the reaction mixture was added a solution of tert-butyl 7-oxo-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate (2.00 g, 8.3 mmol) in dry THF (20 ml). The resulting mixture was stirred at 80° C. overnight. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic phase was dried, concentrated and purified by silica gel chromatography to give tert-butyl 7-(2-ethoxy-2-oxo-ethylidene)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate 123b (1.20 g, 46.5%) and tert-butyl 7-(2-ethoxy-2-oxo-ethyl)-3-oxa-9-azabicyclo[3.3.1]non-6-ene-9-carboxylate 123e (0.800 g, 30.8%). Compound 123b: 1H NMR (400 MHz, CDCl3): d=5.72-5.66 (m, 1H), 4.29-4.23 (m, 1H), 4.15 (d, J=7.3 Hz, 3H), 4.05-3.97 (m, 1H), 3.88-3.77 (m, 2H), 3.76-3.65 (m, 2H), 2.77-2.61 (m, 1H), 2.38 (d, J=15.3 Hz, 2H), 1.53-1.48 (m, 9H), 1.30-1.26 (m, 3H).

Workup

  1. temperatureheated at 80° C. for 20 mins
  2. temperatureThe reaction mixture was cooled down to room temperature
  3. stirringThe resulting mixture was stirred at 80° C. overnight
  4. customThe solvent was removed
  5. customthe residue was partitioned between ethyl acetate and water
  6. customThe organic phase was dried
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-543137f5c311425c854c2f43b987c196
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

Loading…