Methanesulfonic Acid → Ethyl 7-oxoazepane-4-carboxylate

HRID 1452513Notes

Reaction equation

HRID 1452513 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.[N-:13]=[N+]=[N-].[Na+].CS(O)(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[O:1]=[C:2]1[NH:13][CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 33557Sodium AzideHCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 23093698Ethyl 7-oxoazepane-4-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
10 °C

Procedure

In a 250 ml three necked flask fitted with reflux condenser, magnetic stirrer and dropping funnel under inert atmosphere, 5.6 ml (5.98 g, 34 mmoles, 1 eq) of ethyl 4-oxocyclohexanecarboxylate 27 were dissolved in 50 ml of CHCl3. 6.65 g (102 mmole, 3 eq) of sodium azide were added, followed by 22.1 ml (32.8 g, 341 mmoles, 10 eq) of methanesulfonic acid dissolved in 20 ml of over 30 min. The mixture was heated to reflux for 1 hour and cooled down to 10° C. 200 ml of saturated sodium bicarbonate solution were added, the mixture decanted and the aqueous phase extracted with 3×150 ml of CHCl3, the combined organic phases were dried over magnesium sulfate, filtered and concentrated to dryness. The residue was purified by PrepLC (800 g SiO2, CH2Cl2/MeOH, 97/3) to give 5.1 g of crude compound. It was crystallised from 40 ml of diethylether to give 4.41 g of pure ester 28, 70% yield.

Workup

  1. temperaturewith reflux condenser, magnetic stirrer
  2. dissolutiondissolved in 20 ml of over 30 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 1 hour
  5. customthe mixture decanted
  6. extractionthe aqueous phase extracted with 3×150 ml of CHCl3
  7. dry with materialthe combined organic phases were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue was purified by PrepLC (800 g SiO2, CH2Cl2/MeOH, 97/3)
  11. customto give 5.1 g of crude compound
  12. customIt was crystallised from 40 ml of diethylether

Sources & evidence

ORD record
ord-416b106a27ca4e21ab83ee08325425e7
Source dataset
uspto-grants-2009_01
Patent number
US07473697B2

Reaction notes

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