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

HRID 1096171Notes

Reaction equation

HRID 1096171 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>C(Cl)Cl>[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 CH2Cl2 (910 ml) was added a solution of dimethylsulfoxide (68.24 ml, 0.961 mol) in CH2Cl2 (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 CH2Cl2 (910 ml) was added within 40 min keeping the internal temperature at below −60° C. 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. NaCl solution (3 l) and evaporated. The residual orange powder was dissolved in TBME (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 TBME (300 ml) and purified by filtration over silica gel (700 g) using a 3:1 heptane/TBME 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%), GC purity 100a %.

Workup

  1. customat below −60° C
  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. NaCl solution (3 l)
  8. customevaporated
  9. dissolutionThe residual orange powder was dissolved in TBME (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-0224370874f34562ad09e3d51a9e67d6
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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