Sodium Thiosulfate → tert-Butyl 4-oxo-6-azaspiro[2.5]octane-6-carboxylate

HRID 1096170Notes

Reaction equation

HRID 1096170 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]2([CH2:13][CH2:12]2)[CH:10]([OH:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].[Na+].C(=O)(O)[O-].[Na+].Cl[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl.CC1(C)N([O])C(C)(C)CCC1>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]2([CH2:13][CH2:12]2)[C:10](=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 23665760Sodium Hypochlorite2×HCID 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 100.1%

Reagents, catalysts & solvents 2

HCID 2724126TempoCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of 4-hydroxy-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (20.0 g, 88.0 mmol) in CH2Cl2 (170 ml) was added sodium bromide (1.092 g, 10.6 mmol), sodium bicarbonate (2.439 g, 29.0 mmol) and 2,2,6,6-tetramethylpiperidine 1-oxyl (237.1 mg, 1.49 mmol). The mixture was cooled to −5° C. and sodium hypochlorite solution (9.5% in water, 55.16 ml) was added within 10 min resulting in a red coloration and a temperature rise to 9° C. The mixture was stirred for 35 min at 0-5° C. and, as conversion was incomplete (2.5% starting material remaining), additional sodium hypochlorite solution (9.5% in water, 7.0 ml) was added within 30 min and the mixture stirred for another 30 min at 0° C. GC analysis indicated complete conversion (<0.1% starting material remaining). Sodium thiosulfate solution (10% in water, 100 ml) was added within 10 min resulting in decoloration. The organic phase was separated, washed with water (100 ml), dried over sodium sulfate (50 g), filtered and evaporated (15 mbar, 40° C.) to afford 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester as yellowish powder (19.84 g), GC purity 99a %. The powder was dissolved in warm TBME (20 ml), heptane (60 ml) was added to induce crystallization and the white suspension stirred at 0-5° C. for 1.5 h. Filtration, washing with heptane (20 ml) and drying (10 mbar, 45° C.) afforded 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (17.25 g, 87%) as white crystalline material, GC purity 100a %. 1H-NMR (CDCl3, 300 MHz): 4.08 (s, CH2 (5)), 3.66 (m, CH2 (7)), 1.88 (m, CH2 (8)), 1.48 (s, tert-Bu), 1.40 (m, 2H), 0.81 (m, 2H).

Workup

  1. customresulting in a red coloration
  2. customto 9° C
  3. additionwas added within 30 min
  4. stirringthe mixture stirred for another 30 min at 0° C
  5. customresulting in decoloration
  6. customThe organic phase was separated
  7. washwashed with water (100 ml)
  8. dry with materialdried over sodium sulfate (50 g)
  9. filtrationfiltered
  10. customevaporated (15 mbar, 40° C.)

Sources & evidence

ORD record
ord-bfd0ae91e32f48b4835d3cfa7b3748cd
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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