Hydroxyamine hydrochloride → 4-(6-Amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1822008Notes

Reaction equation

HRID 1822008 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21]=C(C3C=CC=CC=3)C3C=CC=CC=3)[N:16]=2)[CH2:10][CH:9]1[CH3:35])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[Na+].Cl.NO>CO>[NH3:8].[CH3:1][OH:5].[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[N:16]=2)[CH2:10][CH:9]1[CH3:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 767271984-[6-(Benzhydrylidene-amino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 21705897Ammonia methanolHCID 690712164-(6-Amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 4-[6-(benzhydrylidene-amino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl ester cis isomer 1 (preparation 61), methanol (150 mL), sodium acetate (2.54 g, 30.94 mmol), and hydroxylamine monohydrogen chloride (1.61 g, 23.2 mmol) and stir. After 30 min., partition between 0.25 M sodium hydroxide solution (100 mL) and 1:1 hexane:ethyl acetate (300 mL). Combine organic layers, wash with aqueous NaCl solution, dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 9:1:0.2 hexane:ethyl acetate:2M ammonia/methanol to obtain the title compound (2.81 g, 70%). 1H NMR (CDCl3): 7.3 (dd, 1H), 6.05 (m, 2H), 5.3 (m, 1H), 4.3 (m, 1H), 4.25 (bs, 2H), 3.85 (m, 1H), 3.25 (m, 1H), 1.9 (m, 3H), 1.7 (m, 1H), 1.5 (s, 9H), 1.3 (d, 3H).

Workup

  1. custompartition between 0.25 M sodium hydroxide solution (100 mL) and 1:1 hexane
  2. washCombine organic layers, wash with aqueous NaCl solution
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the residue by silica gel flash chromatography
  7. washeluting with 9:1:0.2 hexane

Sources & evidence

ORD record
ord-e310bc1adb2947e8869685e2eff9e532
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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