p-Toluenesulfonic acid → HCID 70856308, compound

HRID 1850800Notes

Reaction equation

HRID 1850800 reaction equation
[C:1]([N:3]1[CH2:8][CH2:7][CH:6]([C@H:9]2[CH2:11][C@H:10]2[CH2:12][CH2:13][O:14][C:15]2[N:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:17][C:16]=2[CH3:29])[CH2:5][CH2:4]1)#[N:2].[OH:30][NH:31][C:32](=N)[CH:33]([CH3:35])[CH3:34].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.[Cl-].[Zn+2].[Cl-]>[CH:33]([C:32]1[N:2]=[C:1]([N:3]2[CH2:4][CH2:5][CH:6]([C@H:9]3[CH2:11][C@H:10]3[CH2:12][CH2:13][O:14][C:15]3[N:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])=[CH:17][C:16]=3[CH3:29])[CH2:7][CH2:8]2)[O:30][N:31]=1)([CH3:35])[CH3:34]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 86711214HCID 86711214, compoundHCID 178449908HCID 178449908, compound

Product 1

HCID 70856308HCID 70856308, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of tert-butyl (6-{2-[(1S,2R)-2-(cyanopiperidin-4-yl)cyclopropyl]ethoxy}-5-methylpyridin-3-yl)acetate (650 mg, 1.63 mmol), N-hydroxy-2-methylpropanimidamide (1.38 eq., 230 mg) and zinc chloride (1.58 eq., 350 mg) in 5 mL of DMF was stirred 2 hrs at 80° C., then PTSA (1.0 eq, 280 mg) was added and stirred for additional 2 hrs at 85° C. The mixture was cooled to room temperature and then quenched by said aq soln of NaHCO3. The mixture was extracted with EtOAc (2×75 mL), and the combined organics were then washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by ISCO column (40 g silica gel) using ethyl acetate in hexane (0-40% EA, 400 ml, and 40-100% EA 200 ml) to give the product. LCMS (ESI) m/z 485 [M+H]+.

Workup

  1. stirringstirred for additional 2 hrs at 85° C
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched
  4. extractionThe mixture was extracted with EtOAc (2×75 mL)
  5. washthe combined organics were then washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. customThe residue was purified by ISCO column (40 g silica gel)
  10. customto give the product

Sources & evidence

ORD record
ord-87a86c4f3eae44ccb462c554c5cae166
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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