Azetidine → (2S,3R)-1-t-butyldimethylsilyl-3-azido-4-oxo-2-azetidinecarboxylic acid

HRID 1783437Notes

Reaction equation

HRID 1783437 reaction equation
[Li+].CC([N-]C(C)C)C.[Si:9]([N:16]1[C:19](=[O:20])[CH2:18][C@H:17]1[C:21]([OH:23])=[O:22])([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].N1CCC1.CC(C1C=C(C(C)C)C(S([N:43]=[N+:44]=[N-:45])(=O)=O)=C(C(C)C)C=1)C>C1COCC1>[N:43]([C@H:18]1[C:19](=[O:20])[N:16]([Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[C@@H:17]1[C:21]([OH:23])=[O:22])=[N+:44]=[N-:45]

Participants

6

Reactant 4

HCID 10422AzetidineHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 2724682Lithium diisopropylamideHCID 10489602(2S)-1-[tert-Butyl(dimethyl)silyl]-4-oxoazetidine-2-carboxylic acid

Product 1

HCID 13712291(2S,3R)-1-t-butyldimethylsilyl-3-azido-4-oxo-2-azetidinecarboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-10 °C

Procedure

To LDA (1.8M, 4.99 mL) and THF (10 mL) at −78° C. was added dropwise (S)-1-t-butyldimethylsilyl-4-oxo-2-azetidinecarboxylic acid (4, 1.0 g) in THF (15 mL). The resulting solution was warmed to −30° C. or −10° C. for 30 min. If a slurry formed, additional THF was added to solublize the azetidine. After 30 min., the solution was cooled to −78° C. A pre-cooled solution (−10° C.) of trisyl azide (1.61 g) in THF (10 mL) was added slowly. The reaction mixture was stirred for one hour before quenching with TMSCl (0.82 mL). The cold bath was then removed and the solution allowed to stir for an additional hour. Saturated sodium bicarbonate (100 mL) was added and the aqueous layer was extracted with diethyl ether (2×100 mL). The organic extracts were discarded. The aqueous layer was then brought to pH=7 by slow addition of 1N HCl and extracted with Et2O (2×100 mL) and the organic layers were discarded. The aqueous layer was then brought to pH=3 by slow addition of 1N HCl and extracted with EtOAc (3×100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to yield 131 which was taken on to the next step without further purification.

Workup

  1. customIf a slurry formed
  2. temperaturethe solution was cooled to −78° C
  3. custombefore quenching with TMSCl (0.82 mL)
  4. customThe cold bath was then removed
  5. stirringto stir for an additional hour
  6. additionSaturated sodium bicarbonate (100 mL) was added
  7. extractionthe aqueous layer was extracted with diethyl ether (2×100 mL)
  8. additionThe aqueous layer was then brought to pH=7 by slow addition of 1N HCl
  9. extractionextracted with Et2O (2×100 mL)
  10. additionThe aqueous layer was then brought to pH=3 by slow addition of 1N HCl
  11. extractionextracted with EtOAc (3×100 mL)
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e223992e05b5407da52f7f612971053b
Source dataset
uspto-grants-2009_03
Patent number
US07501404B2

Reaction notes

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