N,O-Dimethylhydroxylamine → (3RS,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide

HRID 2191106Notes

Reaction equation

HRID 2191106 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](O)=[O:15])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([C:27]([O:31][N:32]1N=NC2C=CC=N[C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CNOC.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:27][O:31][N:32]([CH3:33])[C:14]([CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH:10]1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)=[O:15]

Participants

6

Reactant 4

HCID 14232N,O-DimethylhydroxylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68479302(3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid

Product 1

HCID 72299147(3RS,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 mL round bottom flask with a magnetic stirrer 900 mg (2.72 mmol) (3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid and 1.14 g (3 mmol) HATU was dissolved in 20 mL dry DMF. The greenish solution was stirred for 15 min, 320 mg (3.28 mmol) N,O-dimethylhydroxylamine hydrochlorideowed and 2.32 mL DIPEA was added. The mixture was stirred for 3 h at room temperature and concentrated under high vacuum. The green viscous oil was taken up in 60 mL ethyl acetate and 75 mL 5% aqueous NaHCO3-solution. The aqueous layer was separated and extracted once with 60 mL ethyl acetate. The combined organic layers were washed with 75 mL 1% AcOH/water-solution and once with 100 ml brine, dried over Na2SO4, filtered off and concentrated under vacuum. The residue was purified over silica eluting with a gradient formed from ethyl acetate/heptane to yield after evaporation of the product containing fractions 990 mg (97%) of the title compound as colorless viscous oil. MS (m/e): 373.3 [(M+H)+].

Workup

  1. stirringThe mixture was stirred for 3 h at room temperature
  2. concentrationconcentrated under high vacuum
  3. customThe aqueous layer was separated
  4. extractionextracted once with 60 mL ethyl acetate
  5. washThe combined organic layers were washed with 75 mL 1% AcOH/water-solution and once with 100 ml brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered off
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified over silica eluting with a gradient
  10. customformed from ethyl acetate/heptane
  11. customto yield
  12. customafter evaporation of the product
  13. additioncontaining fractions 990 mg (97%) of the title compound as colorless viscous oil

Sources & evidence

ORD record
ord-b29f14e8dbf04e1d8d57180cd9613c13
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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