HCID 123957772, compound → HCID 123292264, compound

HRID 1481617Notes

Reaction equation

HRID 1481617 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)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][Mg+].[Br-]>C1COCC1>[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]([OH:19])[CH3:29])[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)[CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 123957772HCID 123957772, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 123292264HCID 123292264, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6S,7aR)-6-(benzyloxy)-5-formyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.920 g, 2.26 mmol) in anhydrous THF (20 mL) at 15° C. was added a solution of MeMgBr (1.4 M in THF/toluene, 4.1 mL, 5.7 mmol) dropwise. The reaction mixture was stirred at room temperature for 3 h, and then quenched with saturated aqueous NaHCO3 solution (30 mL). The mixture was extracted with EtOAc (2×30 mL), and the combined extracts were dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by automatic flash column chromatography (MeOH/DCM, 0:4 to 1:4), affording tert-butyl ((3aR,5R,6S,7aR)-6-(benzyloxy)-5-(1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.350 g, 37%) as a white foam; 1H NMR (400 MHz, CDCl3) for this material indicated that it contained two diastereomers with a ratio of 1:2. Also isolated was the deprotected side product 1-((3aR,5R,6S,7aR)-6-(benzyloxy)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)ethanol (0.300 g, 41%) as a white solid; 1H NMR (400 MHz, CDCl3) for this material indicated that it contained two diastereomers with a ratio of 1:1.4.

Workup

  1. customquenched with saturated aqueous NaHCO3 solution (30 mL)
  2. extractionThe mixture was extracted with EtOAc (2×30 mL)
  3. dry with materialthe combined extracts were dried over anhydrous Na2SO4
  4. filtrationAfter filtration the solvent
  5. customwas evaporated under reduced pressure
  6. customthe residue was purified on silica gel by automatic flash column chromatography (MeOH/DCM, 0:4 to 1:4)

Sources & evidence

ORD record
ord-5576b6d2665b462eb5cf555ae861e9e0
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

Loading…