Di-tert-butyl dicarbonate → HCID 123992840, compound

HRID 1481625Notes

Reaction equation

HRID 1481625 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]=[O:19])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:14]2)[C@@H:10]1[F:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Mg+].[Br-].[CH3:33]C(OC(OC(OC(C)(C)C)=O)=O)(C)C>C1COCC1.CCOCC>[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]([OH:19])[CH3:33])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[S:14]2)[C@@H:10]1[F:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 123295653HCID 123295653, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 123992840HCID 123992840, compoundYield 48.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-formyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (2.0 g, 4.7 mmol) in anhydrous THF (40 mL), at 0° C. and under N2, was added MeMgBr (1.4 M in THF/toluene, 8.0 mL, 11.2 mmol). After addition the mixture was stirred at room temperature for 3 h. The reaction was diluted with Et2O (50 mL) and then quenched with saturated NaHCO3 aqueous solution (50 mL). The organic layer was collected, and the aqueous was extracted with DCM (3×40 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was dissolved in DCM (40 mL) and Boc2O (2.0 g, 9.2 mmol) was added. The mixture was stirred at room temperature for 16 h. After concentration the residue was purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:2 to 3:2), affording tert-butyl ((3aR,5R,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-(1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (1.0 g, 48%), as a mixture of diastereomers.

Workup

  1. additionAfter addition the mixture
  2. customquenched with saturated NaHCO3 aqueous solution (50 mL)
  3. customThe organic layer was collected
  4. extractionthe aqueous was extracted with DCM (3×40 mL)
  5. extractionThe combined extract
  6. dry with materialwas dried over anhydrous Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas evaporated under reduced pressure
  9. dissolutionthe residue was dissolved in DCM (40 mL)
  10. stirringThe mixture was stirred at room temperature for 16 h
  11. concentrationAfter concentration the residue
  12. customwas purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:2 to 3:2)

Sources & evidence

ORD record
ord-2f747bbe5c2a406887123123b801bd39
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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