Tetraethyl methylenediphosphonate → HCID 57554734, compound

HRID 1511902Notes

Reaction equation

HRID 1511902 reaction equation
[H-].[Na+].[CH2:3]([P:12](=[O:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])P(=O)(OCC)OCC.[CH:20]([C@@:22]1([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:26][CH2:25][C@H:24]([C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:29][CH:28]=2)[CH2:23]1)=O>C1COCC1>[CH2:17]([O:16][P:12](/[CH:3]=[CH:20]/[C@@:22]1([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:26][CH2:25][C@H:24]([C:27]2[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:31][CH:32]=2)[CH2:23]1)([O:13][CH2:14][CH3:15])=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 15455Tetraethyl methylenediphosphonateHCID 24758Sodium hydrideHCID 57554657HCID 57554657, compound

Product 1

HCID 57554734HCID 57554734, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.020 g, 0.498 mmol) (Aldrich) was stirred in THF (3.32 ml) under nitrogen to give a colorless suspension. Tetraethyl methylenediphosphonate (0.124 ml, 0.498 mmol) (ALDRICH) was added and the reaction stirred for about 30 min. Tert-butyl (1R,3S)-1-formyl-3-(4-octylphenyl)cyclopentylcarbamate (0.2 g, 0.498 mmol) was added in small portions and the reaction stirred for about 16 h. Solvents were removed under reduced pressure. Ethyl acetate (50 mL) and water (10 mL) were added and the layers separated and extracted with ethyl acetate (2×10 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a yellow oil. The residue was purified by flash column chromatography (40 g Redi-Sep) eluting with ethyl acetate/heptane and the product fractions combined. The solvent was removed under reduced pressure to provide tert-butyl (1R,3S)-1-((E)-2-(diethoxyphosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.237 g, 0.442 mmol, 89% yield) as an orange oil: LC/MS (method f) Rt=3.12 min.; MS m/z: 553.42 (M+H2O)+.

Workup

  1. customto give a colorless suspension
  2. stirringthe reaction stirred for about 16 h
  3. customSolvents were removed under reduced pressure
  4. additionEthyl acetate (50 mL) and water (10 mL) were added
  5. customthe layers separated
  6. extractionextracted with ethyl acetate (2×10 mL)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to a yellow oil
  11. customThe residue was purified by flash column chromatography (40 g Redi-Sep)
  12. washeluting with ethyl acetate/heptane
  13. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-bbd130f778574255b8a7882c8a6fbc00
Source dataset
uspto-grants-2012_07
Patent number
US08217027B2

Reaction notes

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