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

HRID 2280156Notes

Reaction equation

HRID 2280156 reaction equation
FC(F)(F)C([O-])=O.[C:8]([C:10]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][CH:21]=[CH:20][C:11]=1[O:12][CH2:13][C@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][NH2+:15]1)#[N:9].C(N(CC)CC)C.[N:34]1[CH:39]=[CH:38][C:37]([CH2:40][NH:41][C:42](=O)[O:43]C2C=CC([N+]([O-])=O)=CC=2)=[CH:36][CH:35]=1.O>ClCCl>[C:8]([C:10]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][CH:21]=[CH:20][C:11]=1[O:12][CH2:13][C@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][N:15]1[C:42]([NH:41][CH2:40][C:37]1[CH:38]=[CH:39][N:34]=[CH:35][CH:36]=1)=[O:43])#[N:9]

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine3×HCID 86714290(R)-2-((2-cyano-3-nitrophenoxy)methyl)piperidin-1-ium 2,2,2-trifluoroacetateHCID 867143034-Nitrophenyl pyridin-4-ylmethylcarbamate2×

Product 1

HCID 86714302(R)-2-((2-cyano-3-nitrophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamideYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-2-((2-cyano-3-nitrophenoxy)methyl)piperidinium 2,2,2-trifluoroacetate (Example 16c, 1.12 g, 2.99 mmol) in dichloromethane (5 mL), was added triethylamine (420 uL, 3.01 mmol). To that mixture was added a suspension of 4-nitrophenyl pyridin-4-ylmethylcarbamate (Example 27d, 980 mg, 3.59 mmol) in dichloromethane (5 mL), followed by triethylamine (420 uL, 3.01 mmol). After stirring for 23 h at room temperature, additional portions of 4-nitrophenyl pyridin-4-ylmethylcarbamate (980 mg, 3.59 mmol) and triethylamine (420 uL, 3.01 mmol) were added, and the resulting reaction mixture was stirred for 1 h. at which time it was poured into water, and washed successively with saturated aqueous NaHCO3 water and brine, dried over MgSO4, filtered, concentrated and purified by flash chromatography (0-100% ethyl acetate in hexanes followed by 0-10% methanol in dichloromethane) to provide (R)-2-((2-cyano-3-nitrophenoxy)methyl)-N-(pyridin-4-ylmethyl)piperidine-1-carboxamide (365 mg, 32%). MS=396 (MH+).

Workup

  1. additionTo that mixture was added
  2. customthe resulting reaction mixture
  3. stirringwas stirred for 1 h. at which time it
  4. washwashed successively with saturated aqueous NaHCO3 water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography (0-100% ethyl acetate in hexanes followed by 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-5ef07cd9c3364e97951f702b356583f0
Source dataset
uspto-grants-2015_09
Patent number
US09138013B2

Reaction notes

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