Di-tert-butyl dicarbonate → HCID 123795628, compound

HRID 1481612Notes

Reaction equation

HRID 1481612 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>[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

5

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 123454875HCID 123454875, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 123795628HCID 123795628, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6R,7R,7aR)-6-(benzyloxy)-7-fluoro-5-formyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.930 g, 2.19 mmol) in anhydrous THF (15 mL), at 0° C. and under N2, was added MeMgBr (1.4 M in THF/toluene, 3.0 mL, 5.2 mmol). After addition the mixture was stirred at room temperature for 3 h. The reaction was quenched with saturated aqueous NaHCO3 solution (30 mL), and then extracted with EtOAc (3×30 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, 1:10 to 1:2), affording tert-butyl ((3aR,5R,6R,7R,7aR)-6-(benzyloxy)-7-fluoro-5-(1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate as an off-white foam (0.767 g, 80%), which contained two diastereomers.

Workup

  1. additionAfter addition the mixture
  2. customThe reaction was quenched with saturated aqueous NaHCO3 solution (30 mL)
  3. extractionextracted with EtOAc (3×30 mL)
  4. extractionThe combined extract
  5. dry with materialwas dried over anhydrous Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas evaporated under reduced pressure
  8. dissolutionthe residue was dissolved in DCM (40 mL)
  9. stirringThe mixture was stirred at room temperature for 16 h
  10. concentrationAfter concentration the residue
  11. customwas purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:10 to 1:2)

Sources & evidence

ORD record
ord-740c44b8b58a43cc90e6f57063ab5e1d
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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