Diisopropylethylamine → tert-butyl (2R,3R,4S)-5-azido-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamate

HRID 879151Notes

Reaction equation

HRID 879151 reaction equation
[N:1]([CH2:4][C@H:5]([CH3:29])[C@H:6]([C@H:15]1[CH2:19][O:18]C(C)(C)[N:16]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])=[N+:2]=[N-:3].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.CCN(C(C)C)C(C)C.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>CCO>[N:1]([CH2:4][C@H:5]([CH3:29])[C@@H:6]([O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:10])[C@H:15]([NH:16][C:22](=[O:23])[O:24][C:25]([CH3:28])([CH3:26])[CH3:27])[CH2:19][OH:18])=[N+:2]=[N-:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 59226479(R)-tert-butyl 4-((1R,2S)-3-azido-1-(tert-butyldimethylsilyloxy)-2-methylpropyl)-2,2-dimethyloxazolidine-3-carboxylate

Product 1

HCID 86639730tert-butyl (2R,3R,4S)-5-azido-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamateYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (R)-tert-butyl 4-((1R,2S)-3-azido-1-(tert-butyldimethylsilyloxy)-2-methylpropyl)-2,2-dimethyloxazolidine-3-carboxylate (1.0 equiv.) in EtOH (0.1 M) was added PPTS (1.3 equiv.) and the mixture was refluxed for 2 days. The volatiles were removed under vacuo, the residue was dissolved in DCM (0.1 M) and DIEA (1.5 equiv.) and Boc2O (1.0 equiv.) were added to the reaction mixture. The solution was stirred for 3 hours at room temperature. The solvents were removed under reduced pressure and the residue was diluted with ethyl acetate, washed with water, aqueous NaHSO4, aqueous NaHCO3, sat. NaCl, the organic phase was dried with magnesium sulfate, filtered, and concentrated. The residue was purified via silica gel column chromatography eluting with ethyl acetate and hexanes (1:3) to give tert-butyl (2R,3R,4S)-5-azido-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamate as the major isomer (5:2) in 70% yield. LC/MS=289.3 (M+H-Boc), Rt=0.76 min (Frac 65%-95% method).

Workup

  1. temperaturethe mixture was refluxed for 2 days
  2. customThe volatiles were removed under vacuo
  3. dissolutionthe residue was dissolved in DCM (0.1 M)
  4. customThe solvents were removed under reduced pressure
  5. additionthe residue was diluted with ethyl acetate
  6. washwashed with water, aqueous NaHSO4, aqueous NaHCO3, sat. NaCl
  7. dry with materialthe organic phase was dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified via silica gel column chromatography
  11. washeluting with ethyl acetate and hexanes (1:3)

Sources & evidence

ORD record
ord-343db4e8a1bf4e4789148b1cbd7d8629
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

Loading…