(R)-2-((2-cyano-3-nitrophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamide → (R)-2-((3-amino-2-cyanophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamide

HRID 332980Notes

Reaction equation

HRID 332980 reaction equation
[C:1]([C:3]1[C:26]([N+:27]([O-])=O)=[CH:25][CH:24]=[CH:23][C:4]=1[O:5][CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][CH2:9][N:8]1[C:13]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1)=[O:14])#[N:2]>C1COCC1.C(O)(=O)C.[Fe]>[NH2:27][C:26]1[C:3]([C:1]#[N:2])=[C:4]([CH:23]=[CH:24][CH:25]=1)[O:5][CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][CH2:9][N:8]1[C:13]([NH:15][CH2:16][C:17]1[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=1)=[O:14]

Participants

4

Reactant 1

HCID 86714302(R)-2-((2-cyano-3-nitrophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamide

Product 1

HCID 86714301(R)-2-((3-amino-2-cyanophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamideYield 40%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 23444217Acetic acid tetrahydrofuranSolvent

Procedure

To a solution of (R)-2-((2-cyano-3-nitrophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamide (Example 27c, 365 mg, 0.98 mmol) in THF/acetic acid (20 mL, 1:1), was added iron powder (164 mg, 2.94 mmol). The reaction was heated to reflux over 15 min under nitrogen, and stirred at reflux for 30 min. Upon completion, the reaction was cooled to room temperature, concentrated, diluted with ethyl acetate and successively washed a saturated solution of NaHCO3, dried over Na2SO4, filtered, concentrated and flash chromatographed (0-10% methanol in dichloromethane) to provide the desired product (141 mg, 40%). MS=366 (MH+).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux over 15 min under nitrogen
  3. temperatureat reflux for 30 min
  4. concentrationconcentrated
  5. additiondiluted with ethyl acetate
  6. washsuccessively washed a saturated solution of NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customflash chromatographed (0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7cc608acad2b47d6ace7731e3309ecd3
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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