N-Hydroxyacetamidine → HCID 58487604, compound

HRID 532977Notes

Reaction equation

HRID 532977 reaction equation
[F:1][C:2]1([C:15]([O:17]CC)=O)[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[C:20](=[N:23]O)([NH2:22])[CH3:21].C[O-].[Na+]>O1CCCC1>[F:1][C:2]1([C:15]2[O:17][N:23]=[C:20]([CH3:21])[N:22]=2)[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:3]1

Participants

5

Reactant 3

HCID 30926N-HydroxyacetamidineHCID 10942334Sodium MethoxideHCID 49761218HCID 49761218, compound

Product 1

HCID 58487604HCID 58487604, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The mixture of 1-tert-butyl 3-ethyl 3-fluoropiperidine-1,3-dicarboxylate 33 and 1a,b (0.8 g, 0.0029 mol) and acetamide oxime (0.54 g, 0.0073 mol) were dissolved in 30 mL tetrahydrofuran. Sodium methoxide (0.79 g, 0.0146 mol) was added and the mixture was heated at reflux for 1.75 hours. The mixture was concentrated and partitioned between water (25 mL) and ethyl acetate (1×100 mL). The aqueous layer was extracted with an additional 50 mL ethyl acetate. The combined organics were washed with 1×25 mL water, 1×40 mL saturated sodium chloride, and dried over Na2SO4. The dried organics were evaporated to an oil. The residue was chromatographed to remove 1a,b with 15 g silica gel, 100% dichloromethane to 5% ethyl acetate/dichloromethane, to obtain 0.18 g of clear colorless oil. MS (ESI) m/z 324 [M+K]+. 1H NMR (CDCl3) δ 1.45 (s, 9H), 1.55-62 (m, 1H), 1.70-1.74 (d, 1H), 1.92-1.95 (m, 1H), 2.17 (m. 1H), 2.29-2.32 (m, 1H), 2.43 (s, 3H), 3.06-3.12 (m, 1H), 3.89-3.92 (m, 2H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 1.75 hours
  3. concentrationThe mixture was concentrated
  4. custompartitioned between water (25 mL) and ethyl acetate (1×100 mL)
  5. extractionThe aqueous layer was extracted with an additional 50 mL ethyl acetate
  6. washThe combined organics were washed with 1×25 mL water, 1×40 mL saturated sodium chloride
  7. dry with materialdried over Na2SO4
  8. customThe dried organics were evaporated to an oil
  9. customThe residue was chromatographed
  10. customto remove 1a,b with 15 g silica gel, 100% dichloromethane to 5% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-7fb640f3cad44f8ba0f3c27d30c0668d
Source dataset
uspto-grants-2014_10
Patent number
US08853219B2

Reaction notes

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