Sodium hydride → HCID 117697992, compound

HRID 1778511Notes

Reaction equation

HRID 1778511 reaction equation
[H-].[Na+].COP([CH2:9][C:10]([O:12][CH3:13])=[O:11])(OC)=O.[F:14][CH:15]1[C:22](=O)[CH2:21][CH:20]2[N:24](C(OCC3C=CC=CC=3)=O)[CH:16]1[CH2:17][O:18][CH2:19]2>O1CCCC1>[F:14][CH:15]1[CH:22]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:21][CH:20]2[NH:24][CH:16]1[CH2:17][O:18][CH2:19]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 117697540HCID 117697540, compound

Product 1

HCID 117697992HCID 117697992, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
70 °C

Procedure

To a solution of NaH (273 mg, 11.4 mmol) in tetrahydrofuran (30 mL) at 0° C. was added dropwise a solution of methyl 2-dimethoxyphosphorylacetate (2.1 g, 11.4 mmol) in tetrahydrofuran (10 mL). The reaction was stirred at 70° C. for 1 hour and then cooled to 0° C. again. To the reaction mixture was added a solution of benzyl 6-fluoro-7-oxo-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate 100c (1.7 g, 5.7 mmol) in tetrahydrofuran (8 mL). The reaction was allowed to warm up to room temperature and stirred 2 hours. After being quenched with 1 N HCl, the solvent was evaporated under reduced pressure. Ethyl acetate (20 mL) was added. The mixture was washed with water, brine, dried over Na2SO4 and evaporated to dryness. The crude mixture was purified on silica gel, eluted with 0 to 20% EtOAc in hexanes, to give the desired product benzyl (7Z/E)-6-fluoro-7-(2-methoxy-2-oxo-ethylidene)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate 100d (1.8 g, 89%). MS: calc'd (MH+) 350, measured (MH+) 350.

Workup

  1. temperaturecooled to 0° C. again
  2. temperatureto warm up to room temperature
  3. stirringstirred 2 hours
  4. customAfter being quenched with 1 N HCl
  5. customthe solvent was evaporated under reduced pressure
  6. additionEthyl acetate (20 mL) was added
  7. washThe mixture was washed with water, brine
  8. dry with materialdried over Na2SO4
  9. customevaporated to dryness
  10. customThe crude mixture was purified on silica gel
  11. washeluted with 0 to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-633dfc042bc84442a790ee43e11fdc64
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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