Hydrochloric Acid → HCID 121362278, compound

HRID 532523Notes

Reaction equation

HRID 532523 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[S:14][CH2:13][CH:12]([OH:15])[CH2:11][C@@H:10]1[N+:16]([O-])=O.Cl.[OH-].[Na+].[O:22](C(OC(C)(C)C)=O)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=O>CCO.CCOCC.[Zn]>[C:26]([O:25][C:23](=[O:22])[NH:16][C@H:10]1[CH2:11][CH:12]([OH:15])[CH2:13][S:14][C@@H:9]1[C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[F:1])([CH3:29])([CH3:28])[CH3:27]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonate2×HCID 68268574HCID 68268574, compound

Product 1

HCID 121362278HCID 121362278, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

(5S,6R)-6-(2,5-Difluorophenyl)-5-nitrotetrahydro-2H-thiopyran-3-ol 5 (1.75 g, 6.36 mmol) and Zn dust (3.5 g, 53.5 mmol) were suspended in EtOH (50 mL) and cooled in an ice bath. 6N HCl (19.4 mL, 116.4 mmol) was added dropwise over 13 min to give a suspension. After 120 min, 5N NaOH (22.6 mL, 113 mmol) was added to give a heavy suspension. A solution of BOC2O (2.03 mL, 8.84 mmol) in Et2O (42 mL) was then added and the suspension was stirred rapidly in the ice bath. After 120 min, additional BOC2O (200 μL, 0.87 mmol) was added and the solution was slowly warmed to room temperature and stirred for an additional 18 h. The organic phase was decanted and the precipitated solids were extracted with 20% EtOH/EtOAc (4×50 mL), the organic phase was combined and evaporated to give an orange oil. The oil was suspended in 1:1 EtOAc/hexanes and loaded onto a 2.75×30 cm silica gel column eluting with 1:1 EtOAc/hexanes and collecting 8 mL fractions. Fractions containing the product were combined and evaporated to give the title compound.

Workup

  1. temperaturecooled in an ice bath
  2. customto give a suspension
  3. customto give a heavy suspension
  4. waitAfter 120 min
  5. customThe organic phase was decanted
  6. extractionthe precipitated solids were extracted with 20% EtOH/EtOAc (4×50 mL)
  7. customevaporated
  8. customto give an orange oil
  9. washeluting with 1:1 EtOAc/hexanes
  10. customcollecting 8 mL fractions
  11. additionFractions containing the product
  12. customevaporated

Sources & evidence

ORD record
ord-716052b095774a9eb60e0bce7b60765f
Source dataset
uspto-grants-2014_10
Patent number
US08853212B2

Reaction notes

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