Azobisisobutyronitrile → (6S)-5-[(tert-butoxy)carbonyl]-5-azaspiro[2.4]heptane-6-carboxylic acid

HRID 1424674Notes

Reaction equation

HRID 1424674 reaction equation
Br[C:2]1(Br)[C:4]2([CH2:8][C@@H:7]([C:9]([OH:11])=[O:10])[N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:5]2)[CH2:3]1.C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1.CCOC(C)=O>[C:15]([O:14][C:12]([N:6]1[C@H:7]([C:9]([OH:11])=[O:10])[CH2:8][C:4]2([CH2:3][CH2:2]2)[CH2:5]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 6547Azobisisobutyronitrile3×HCID 123134Tris(trimethylsilyl)silane3×HCID 71014840(6S)-1,1-dibromo-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid

Product 1

HCID 39871141(6S)-5-[(tert-butoxy)carbonyl]-5-azaspiro[2.4]heptane-6-carboxylic acidYield 39%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a degassed solution of (6S)-1,1-dibromo-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (580 mg, 1.45 mmol) in toluene (6 mL) was added the tris(trimethylsilyl)silane (1.35 mL, 4.36 mmol, 3.0 eq) and AIBN (24 mg, 0.145 mmol, 0.1 eq). The solution was heated at 110° C. for 3 hours. Another batch of tris(trimethylsilyl)silane (0.45 mL 1.45 mmol, 1.0 eq) and AIBN (10 mg) was added. The solution was heated at 110° C. for 2 more hours. A third batch of tris(trimethylsilyl)silane (0.45 mL 1.45 mmol, 1.0 eq) and AIBN (10 mg) was added. The solution was heated at 110° C. for 2 more hours. After being allowed to cool down, the solution was diluted with EtOAc (5 mL). This organic phase was extracted with aqueous K2CO3 (1 M, 10 mL×3). The combined aqueous extractions were cooled (ice/water) and acidified to pH 2 with concentrated HCl. This acidified aqueous phase was extracted with EtOAc (×3), dried (Na2SO4), filtered and evaporated. The residue was dried under vacuum to afford the desired compound as colorless oil (135 mg, 39%).

Workup

  1. temperatureThe solution was heated at 110° C. for 2 more hours
  2. temperatureThe solution was heated at 110° C. for 2 more hours
  3. temperatureto cool down
  4. extractionThis organic phase was extracted with aqueous K2CO3 (1 M, 10 mL×3)
  5. extractionThe combined aqueous extractions
  6. temperaturewere cooled (ice/water)
  7. extractionThis acidified aqueous phase was extracted with EtOAc (×3)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was dried under vacuum

Sources & evidence

ORD record
ord-07a3939fab474c8985d8c542be98574b
Source dataset
uspto-grants-2015_01
Patent number
US08927739B2

Reaction notes

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