Hydrochloric Acid → Tert-butyl 2-[4-(methoxycarbonyl)benzyl]-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

HRID 1920138Notes

Reaction equation

HRID 1920138 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:8][C:7]2([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH2:6][NH:5]1.Br[CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1.Cl>CN(C)C=O>[CH3:30][O:29][C:27]([C:26]1[CH:31]=[CH:32][C:23]([CH2:22][N:5]2[C:4](=[O:3])[CH2:8][C:7]3([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[CH2:6]2)=[CH:24][CH:25]=1)=[O:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 10015184Tert-butyl 3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 67501914Tert-butyl 2-[4-(methoxycarbonyl)benzyl]-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylateYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

Under an argon atmosphere, to an N,N-dimethylformamide (2 mL) solution of sodium hydride (60%, 94 mg), an N,N-dimethylformamide (4 mL) solution of tert-butyl 3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (514 mg) was added at 0° C. The reaction solution was stirred at 50° C. for one hour. The solution was cooled to 0° C. and then an N,N-dimethylformamide (2 mL) solution of methyl 4-(bromomethyl)benzoate (442 mg) was added. The reaction solution was stirred at 0° C. for 30 minutes. To the reaction solution, 0.5N-hydrochloric acid (20 mL) was added. The aqueous layer was extracted twice with ethyl acetate. The aqueous layer was combined with the organic layer, washed in turn with water and saturated brine, and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→1:2) to obtain the title compound (553 mg) having the following physical properties.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. stirringThe reaction solution was stirred at 0° C. for 30 minutes
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. washwashed in turn with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customAfter removing the anhydrous magnesium sulfate
  7. filtrationby filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→1:2)

Sources & evidence

ORD record
ord-fa7bc0fb97814a8db4d20bfe5a8c501d
Source dataset
uspto-grants-2012_05
Patent number
US08168783B2

Reaction notes

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