Sodium hydride → HCID 59260674, compound

HRID 643268Notes

Reaction equation

HRID 643268 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([N:16]2[CH2:22][C:21]3([CH3:24])[CH2:23][CH:17]2[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20]3)=[O:15])=[CH:10][CH:9]=1)(C)(C)C.[H-].[Na+].Br[CH2:31][CH2:32][O:33][CH3:34]>CN(C=O)C>[CH3:34][O:33][CH2:32][CH2:31][NH:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([N:16]2[CH2:26][C:19]3([CH3:25])[CH2:18][CH:17]2[CH2:23][C:21]([CH3:22])([CH3:24])[CH2:20]3)=[O:15])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 9907515[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester

Product 1

HCID 59260674HCID 59260674, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester (0.5 g, 1.34 mmol) in dry DMF (25 ml) was added sodium hydride (75 mg, 1.88 mmol in 60% mineral oil) and the mixture was stirred for 30 min. 1-Bromo-2-methoxy-ethane (224 mg, 1.61 mmol) was added and the mixture was heated to reflux and allowed to cool to room temperature with stirring. The reaction was quenched by addition of water (20 ml) and extracted with diethyl ether (2×25 ml). The combined organic phases were washed with saturated aqueous ammonium chloride (25 ml), dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in DCM (15 ml) and TFA (10 ml) was added. The resulting mixture was stirred for 5 hrs. at room temperature and evaporated in vacuo. To the residue was added water (10 ml) and diethyl ether (20 ml) and the pH was adjusted to 9 by addition of 1 N sodium hydroxide. The organic phase was separated and dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (silica gel) using EtOAc/heptane (1:1) as eluent. Pure fractions were collected and evaporated to dryness affording 0.3 g (68%) of the title compound as an oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. stirringwith stirring
  4. customThe reaction was quenched by addition of water (20 ml)
  5. extractionextracted with diethyl ether (2×25 ml)
  6. washThe combined organic phases were washed with saturated aqueous ammonium chloride (25 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. dissolutionThe residue was dissolved in DCM (15 ml)
  11. additionTFA (10 ml) was added
  12. stirringThe resulting mixture was stirred for 5 hrs
  13. customat room temperature and evaporated in vacuo
  14. additionTo the residue was added water (10 ml) and diethyl ether (20 ml)
  15. additionthe pH was adjusted to 9 by addition of 1 N sodium hydroxide
  16. customThe organic phase was separated
  17. dry with materialdried (Na2SO4)
  18. filtrationfiltered
  19. customevaporated in vacuo
  20. customThe residue was purified by column chromatography (silica gel)
  21. customPure fractions were collected
  22. customevaporated to dryness

Sources & evidence

ORD record
ord-4fa5ca1fab804663b0a98c49fbe25f28
Source dataset
uspto-grants-2010_04
Patent number
US07700583B2

Reaction notes

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