Di-tert-butyl azodicarboxylate → HCID 11016430, compound

HRID 1668410Notes

Reaction equation

HRID 1668410 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[CH2:9]([C@H:16]1[CH2:20][O:19][C:18](=[O:21])[N:17]1[C:22](=[O:27])[CH2:23][CH2:24][CH2:25]Br)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[N:28]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[N:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>C1COCC1.C(Cl)Cl.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[C:40]([O:39][C:37]([N:28]1[CH2:2][CH2:25][CH2:24][C@@H:23]([C:22]([N:17]2[C@@H:16]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:20][O:19][C:18]2=[O:21])=[O:27])[N:29]1[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])=[O:38])([CH3:43])([CH3:42])[CH3:41]

Participants

7

Reactant 3

HCID 97268Di-tert-butyl azodicarboxylateHCID 2724682Lithium diisopropylamideHCID 57612782HCID 57612782, compound

Product 1

HCID 11016430HCID 11016430, compoundYield 49.3%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of diisopropylamine (0.77 mL, 5.53 mmol) in THF (4 mL) at 0° C. is added BuLi (2.17 mL, 5.42 mmol, 2.5 M in hexane) dropwise. The solution is stirred at 0° C. for 30 minutes to form an LDA solution. The LDA solution is cold to −70° C. and added to a solution of (S)-4-benzyl-3-(4-bromo-butyryl)-oxazolidin-2-one (1.72 g, 5.07 mmol) in THF (4 mL) at −70° C. dropwise. After stirring at −70° C. for 2 hours, a solution of di-t-butyl azodicarboxylate (1.40 g, 6.08 mmol) in CH2Cl2 (4 mL) is added slowly. After stirring at −70° C. for 15 minutes, Bu4NI (0.28 g, 0.76 mmol) is added in one portion. After stirring at −70° C. for 10 minutes, the flask with reaction mixture is moved to a −20° C. bath and stirred overnight (16 hours). The reaction mixture is quenched to ether (50 mL) with buffer solution (50 mL, Ph=7), and the mixture is extracted with ether (3×50 mL). The organic layer is dried over Na2SO4 and concentrated. The crude product is purified by chromatography (hexane/EtOAc:70/30) to give (S)-3-((S)-4-benzyl-2-oxo-oxazolidine-3-carbonyl)-tetrahydro-pyridazine-1,2-dicarboxylic acid di-tert-butyl ester as white solid (1.22 g, 49.3%). (NMR and MS data confirmed, U-3133-55-30).

Workup

  1. customis cold to −70° C.
  2. stirringAfter stirring at −70° C. for 15 minutes
  3. stirringAfter stirring at −70° C. for 10 minutes
  4. customthe flask with reaction mixture
  5. customis moved to a −20° C.
  6. stirringstirred overnight (16 hours)
  7. customThe reaction mixture is quenched to ether (50 mL) with buffer solution (50 mL, Ph=7)
  8. extractionthe mixture is extracted with ether (3×50 mL)
  9. dry with materialThe organic layer is dried over Na2SO4
  10. concentrationconcentrated
  11. customThe crude product is purified by chromatography (hexane/EtOAc:70/30)

Sources & evidence

ORD record
ord-e8c4f9ea370c4fcaa0d6143b55b7256e
Source dataset
uspto-grants-2011_08
Patent number
US07989441B2

Reaction notes

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