Dimethyl Sulfoxide → tert-Butyl 4-oxo-6-azaspiro[2.5]octane-6-carboxylate

HRID 559331Notes

Reaction equation

HRID 559331 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:25][CH2:24][C:21]2([CH2:23][CH2:22]2)[CH:20]([OH:26])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[C:11]([O:15][C:16]([N:18]1[CH2:25][CH2:24][C:21]2([CH2:23][CH2:22]2)[C:20](=[O:26])[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 66782779tert-Butyl 4-hydroxy-6-azaspiro[2.5]octane-6-carboxylate

Product 1

HCID 66783635tert-Butyl 4-oxo-6-azaspiro[2.5]octane-6-carboxylateYield 102%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of oxalyl chloride (42.35 ml, 0.480 mol) in dichloromethane (910 ml) was added a solution of dimethylsulfoxide (68.24 ml, 0.961 mol) in dichloromethane (910 ml) at −70° C. within 45 min. The solution was stirred for 15 min and a solution of 4-hydroxy-6-aza-spiro[2,5]octane-6-carboxylic acid tert-butyl ester (91.00 g, 0.400 mol) in dichloromethane (910 ml) was added within 40 min keeping the internal temperature at below −60°. The mixture was stirred for 35 min and triethylamine (280.4 ml, 2.00 mol) was added at below −60° C. within 10 min. The cooling bath was removed and the yellow suspension was stirred for 1 h then quenched with water (1.4 l). The organic phase was separated, washed with water (3×1 l) and sat. aq. sodium chloride solution (3 l) and evaporated. The residual orange powder was dissolved in tert-butyl methyl ether (1.40 l), the turbid solution filtered (Hyflo Speedex) to remove some insoluble material and the clear filtrate evaporated to provide crude 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester as yellow powder (91.9 g). The material was re-dissolved in tert-butyl methyl ether (300 ml) and purified by filtration over silica gel (700 g) using a 3:1 heptane/tert-butyl methyl ether mixture (6.5 l). Evaporation and drying (10 mbar, 40° C.) afforded 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester as whitish powder (80.58 g, 89%), CC purity 100a %.

Workup

  1. customat below −60°
  2. stirringThe mixture was stirred for 35 min
  3. customThe cooling bath was removed
  4. stirringthe yellow suspension was stirred for 1 h
  5. customthen quenched with water (1.4 l)
  6. customThe organic phase was separated
  7. washwashed with water (3×1 l) and sat. aq. sodium chloride solution (3 l)
  8. customevaporated
  9. dissolutionThe residual orange powder was dissolved in tert-butyl methyl ether (1.40 l)
  10. filtrationthe turbid solution filtered (Hyflo Speedex)
  11. customto remove some insoluble material
  12. customthe clear filtrate evaporated

Sources & evidence

ORD record
ord-2fd6c3b747f542f9b1304950ff15d928
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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