Diethyl Ether → Tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylate

HRID 47339

Reaction equation

HRID 47339 reaction equation
[CH2:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(OCC)C.[Cl:20][C:21](Cl)([Cl:25])[C:22](Cl)=[O:23].C(=O)(O)[O-].[Na+]>C(COC)OC.[Cu].[Zn]>[Cl:20][C:21]1([Cl:25])[C:2]2([CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)[CH2:1][C:22]1=[O:23]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 6420Trichloroacetyl chlorideHCID 516892Sodium BicarbonateHCID 27568081-Boc-4-Methylenepiperidine

Product 1

HCID 9857764Tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylateYield 81.1%

Reagents, catalysts & solvents 2

HCID 10290809Zinc copper coupleCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

49.3 g of tert-butyl 4-methylene-1-piperidine carboxylate was added to a mixture of 157.2 g zinc-copper alloy and 500 ml diethyl ether, and 900 ml solution of 181.8 g trichloroacetyl chloride in dimethoxyethane was added dropwise thereinto over 5.5 hours. After stirred for 30 min, the reaction solution was cooled and saturated aqueous sodium bicarbonate was added thereto at 0° C. or less. The mixture was filtered through Celite and evaporated. The resulting residue was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated, and the resulting residue was subjected to silica gel column chromatography to give 62.5 g of tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylate.

Workup

  1. temperaturethe reaction solution was cooled
  2. customat 0° C. or less
  3. filtrationThe mixture was filtered through Celite
  4. customevaporated
  5. extractionThe resulting residue was extracted with ethyl acetate
  6. washThe extract was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-686052dff0074236bc1ad47101bb61b1
Source dataset
uspto-grants-2004_03
Patent number
US06699870B2

Linked notes

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