Ozone → (S)-tert-butyl 4-((S)-2-((tert-butyldimethylsilyloxy)methyl)-4-hydroxybutyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 451824Notes

Reaction equation

HRID 451824 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]([CH2:26][CH:27]=C)[CH2:11][C@H:12]1[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[N:13]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O:29]=[O+][O-].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C(Cl)Cl.C1COCC1>[Si:1]([O:8][CH2:9][C@H:10]([CH2:26][CH2:27][OH:29])[CH2:11][C@H:12]1[CH2:16][O:15][C:14]([CH3:17])([CH3:18])[N:13]1[C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 24823OzoneHCID 21226445Aluminium lithium hydrideHCID 58011479(S)-tert-Butyl 4-((R)-2-(((tert-butyldimethylsilyl)oxy)methyl)pent-4-en-1-yl)-2,2-dimethyloxazolidine-3-carboxylate

Product 1

HCID 68712820(S)-tert-butyl 4-((S)-2-((tert-butyldimethylsilyloxy)methyl)-4-hydroxybutyl)-2,2-dimethyloxazolidine-3-carboxylateYield 340%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-tert-butyl 4-((R)-2-((tert-butyldimethylsilyloxy)methyl)pent-4-enyl)-2,2-dimethyloxazolidine-3-carboxylate (15 g) in dry CH2Cl2 (250 mL) was treated with a stream of O3 until the reaction mixture turned blue at −78° C. The system was then flushed with O2 to remove excess ozone. Me2S was added and the mixture was allowed to warm to rt. Solvents were removed in vacuo to give the crude product (12 g). The crude product was dissolved in 250 mL of dry THF. The resulting mixture was cooled to 0° C. before LiAlH4 was added. After being stirred for 30 min, the reaction was quenched with 40 mL of H2O followed by 120 mL of 1 N NaOH. The resulting white slurry was filtered through celite, and the clear, colorless filtrate was dried over anhydrous Na2SO4. Filtration followed by concentration in vacuo gave the crude product, which was purified by flash column to give the pure product (S)-tert-butyl 4-((S)-2-((tert-butyldimethylsilyloxy)methyl)-4-hydroxybutyl)-2,2-dimethyloxazolidine-3-carboxylate (5.2 g, 340%). 1H NMR (CDCl3, 400 MHz) δ 0.06 (s, 6H), 0.89 (s, 9H), 1.46 (s, 12H), 1.50 (m, 3H), 1.53 (m, 3H), 3.09 (m, 1H), 3.49 (m, 2H), 3.50 (m, 2H), 3.7 (m, 2H), 3.90 (m, 1H).

Workup

  1. customturned blue at −78° C
  2. customThe system was then flushed with O2
  3. customto remove excess ozone
  4. additionMe2S was added
  5. customSolvents were removed in vacuo
  6. customto give the crude product (12 g)
  7. additionwas added
  8. customthe reaction was quenched with 40 mL of H2O
  9. filtrationThe resulting white slurry was filtered through celite
  10. dry with materialthe clear, colorless filtrate was dried over anhydrous Na2SO4
  11. filtrationFiltration
  12. concentrationfollowed by concentration in vacuo
  13. customgave the crude product, which
  14. customwas purified by flash column

Sources & evidence

ORD record
ord-8bcc8cb2d996432a99a05e601d88838a
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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