1,2-Dichloroethane → tert-butyl (7S)-7-methyl-8-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,8-diazaspiro[2.6]nonane-5-carboxylate

HRID 1808922Notes

Reaction equation

HRID 1808922 reaction equation
[CH2:1]([N:8]1[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10][C@@H:9]1[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH2:25].O[N:27]1[C:31]2C=CC=C[C:30]=2[N:29]=[N:28]1.C(N(CC)CC)C.C(Cl)CCl>CO.CN(C=O)C>[CH3:24][C@@H:9]1[N:8]([C:1](=[O:25])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=2[N:28]2[N:29]=[CH:30][CH:31]=[N:27]2)[CH2:16][C:13]2([CH2:14][CH2:15]2)[CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 70262156tert-butyl (7S)-8-benzyl-7-methyl-5,8-diazaspiro[2.6]nonane-5-carboxylate

Product 1

HCID 59527662tert-butyl (7S)-7-methyl-8-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,8-diazaspiro[2.6]nonane-5-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1.26 g (3.8 mmol) 2-3 in 40 mL MeOH was evacuated under reduced pressure and purged with N2 three times before adding a portion of palladium hydroxide on carbon. After purging three more times with N2, the atmosphere was replaced with H2 and the reaction was stirred under a balloon of H2 for 2 h. The reaction was filtered through a pad of celite by rinsing with EtOAc and MeOH, and the filtrate was concentrated to provide a colorless oil. This material was dissolved in 3 mL of DMF and to it was added 683 mg of 2-4 (3.6 mmol; prepared in an analogous fashion to 1-5, see example 1-C), 668 mg (4.3 mmol) 1-hydroxybenzotriazole hydrate, 1.5 mL (10.8 mmol) triethylamine and 831 mg (4.3 mmol) EDC and the reaction was stirred overnight at 60° C. The reaction was partitioned between EtOAc and 10% aqueous citric acid, the layers were separated, and the organic was washed with water, brine, dried over Na2SO4 and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel (EtOAc/hexanes) to provide 2-5 as a white solid. Data for 2-5: LC/MS: rt=2.36 min; m/z (M+H)=412.3 found; 412.2 required.

Workup

  1. custompurged with N2 three times
  2. additionbefore adding a portion of palladium hydroxide on carbon
  3. customAfter purging three more times with N2
  4. filtrationThe reaction was filtered through a pad of celite
  5. washby rinsing with EtOAc and MeOH
  6. concentrationthe filtrate was concentrated
  7. customto provide a colorless oil
  8. customprepared in an analogous fashion to 1-5
  9. stirringthe reaction was stirred overnight at 60° C
  10. customThe reaction was partitioned between EtOAc and 10% aqueous citric acid
  11. customthe layers were separated
  12. washthe organic was washed with water, brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated by rotary evaporation
  15. customThe residue was purified by column chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-1bdffe1b6a1d4ae8a908cc0bf11eaf83
Source dataset
uspto-grants-2013_01
Patent number
US08362009B2

Reaction notes

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