Methanol → 1-(1-(4-Chlorophenyl)piperidin-4-yl)-2-nitrobutan-1-ol

HRID 453661Notes

Reaction equation

HRID 453661 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[N+:16]([CH2:19][CH2:20][CH3:21])([O-:18])=[O:17].[OH-].[Na+].CO>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([CH:14]([OH:15])[CH:19]([N+:16]([O-:18])=[O:17])[CH2:20][CH3:21])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 79031-NitropropaneHCID 14798Sodium HydroxideHCID 583506941-(4-Chlorophenyl)piperidine-4-carbaldehyde

Product 1

HCID 668426751-(1-(4-Chlorophenyl)piperidin-4-yl)-2-nitrobutan-1-olYield 34.3%

Reagents, catalysts & solvents 2

HCID 8154Hexadecyltrimethylammonium chlorideCatalystHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 1-(4-chlorophenyl)piperidine-4-carbaldehyde (157 mg, 0.7 mmol), 1-nitropropane (0.125 mL, 1.400 mmol), 0.025 M NaOH (2 mL) and MeOH (1 mL) was treated with 25% aqueous cetyltrimethylammonium chloride (0.139 mL, 0.105 mmol). The reaction mixture was sonicated at RT for 4 h, and then stirred at RT for 14 h. After this time, the mixture was treated with brine and extracted with diethyl ether. The extract was dried over MgSO4 and concentrated to yield a residue. The residue was purified by flash chromatography on silica gel, eluting with 15-25% EtOAc/hexanes to give the diastereomeric mixture (2:1 more polar/less polar on reverse-phase HPLC) of the title compound (75 mg, 0.240 mmol, 34.3% yield) as a clear oil. LC-MS: (Waters Sunfire C18 4.6 mm×50 mm) 313.20, [M+H]; tR=1.95 min, 2.21 min; 10%-90%-0.1% MeOH/H2O/TFA to 90%-10%-0.15 MeOH/H2O/TFA at 1n 4 min 4 mL/min flow rate. 1H-NMR (400 MHz, CD3OD) δ ppm 7.05-7.11 (2H, m), 6.81-6.87 (2H, m), 4.42-4.51 (1H, m), 3.67 (2H, dd, J=7.36, 3.84 Hz), 3.61 (3H, d, J=11.42 Hz), 2.51-2.62 (3H, m), 1.81-1.91 (2H, m), 1.58-1.64 (3H, m), 1.51-1.56 (2H, m).

Workup

  1. customThe reaction mixture was sonicated at RT for 4 h
  2. extractionextracted with diethyl ether
  3. dry with materialThe extract was dried over MgSO4
  4. concentrationconcentrated
  5. customto yield a residue
  6. customThe residue was purified by flash chromatography on silica gel
  7. washeluting with 15-25% EtOAc/hexanes

Sources & evidence

ORD record
ord-0f50878af5d44d3c87be70c75cbccbaf
Source dataset
uspto-grants-2013_07
Patent number
US08492550B2

Reaction notes

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