HCID 86711207, compound → HCID 86711208, compound

HRID 1850790Notes

Reaction equation

HRID 1850790 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@@H:7]1[CH2:9][C@@H:8]1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]#[N:17])[CH2:12][CH2:11]1.[OH:26][NH:27][C:28](=N)[CH2:29][O:30][CH3:31]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:23])=[O:24])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@H:7]1[CH2:9][C@H:8]1[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[O:26][N:27]=[C:28]([CH2:29][O:30][CH3:31])[N:17]=2)[CH2:14][CH2:15]1

Participants

5

Reactant 2

HCID 86711207HCID 86711207, compoundHCID 178496050HCID 178496050, compound

Product 1

HCID 86711208HCID 86711208, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-((1R,2S)-2-{2-{2-fluoro-4-(methylsulfonyl)phenoxy]ethyl}cyclopropyl)piperidine-1-carbonitrile (Step D, Example 111; 100 mg, 0.27 mmol) and N-hydroxy-2-methoxyacetimidamide (38 mg, 0.37 mmol) in tetrahydrofuran (5 mL) was added zinc chloride (0.8 mL, 0.5 M in tetrahydrofuran, 0.4 mmol). The mixture was refluxed for 2 h, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in 2 mL of 4N HCl ethanol and water (1:1). The solution was refluxed for 30 min, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in methanol (5 mL), neutralized by the addition of excess potassium carbonate, mixed silica gel (2 g), and concentrated to dryness under reduced pressure. The residue was loaded on a silica gel column (10 g of silica gel) and eluted with a gradient of dichloromethane/CMA, 19:1, 500 mL; 4:1, 500 mL to provide the title compound. MS (ESI) m/z 454 [M+H]+.

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. concentrationconcentrated to dryness under reduced pressure
  3. dissolutionThe residue was dissolved in 2 mL of 4N HCl ethanol
  4. temperatureThe solution was refluxed for 30 min
  5. temperaturecooled to RT
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe residue was dissolved in methanol (5 mL)
  8. additionneutralized by the addition of excess potassium carbonate
  9. additionmixed silica gel (2 g)
  10. concentrationconcentrated to dryness under reduced pressure
  11. washeluted with a gradient of dichloromethane/CMA, 19:1, 500 mL

Sources & evidence

ORD record
ord-4ca24d07ce524cad8ca603b7e6b8a939
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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