Water → 2-{1-[2-Methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}ethanol

HRID 419616Notes

Reaction equation

HRID 419616 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[C:6]([CH3:10])=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12].[NH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][OH:22])[CH2:16][CH2:15]1.C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[CH3:10][C:6]1[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][OH:22])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 739534-PiperidineethanolHCID 184681411-Fluoro-5-methoxy-2-methyl-4-nitrobenzene

Product 1

HCID 594527382-{1-[2-Methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}ethanolYield 95.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To 1-fluoro-2-methyl-5-(methyloxy)-4-nitrobenzene (Example 113, Step B) (21.5 g, 116 mmol) in DMSO (100 mL) was added 2-(4-piperidinyl)ethanol (15 g, 116 mmol) and K2CO3 (48.1 g, 348 mmol). The reaction was heated in a sealed tube at 80° C. overnight. The reaction mixture was cooled to rt and poured into H2O. The resultant solid was filtered, air dried, dissolved in DCM, dried (Na2SO4), filtered, and rotovapped down to give the title compound of Step F (32.6 g, 111 mmol, 95%). 1H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 6.63 (s, 1H), 4.33 (t, J=5.0 Hz, 1H), 3.85 (s, 3H), 3.39-3.49 (m, 2H), 3.23 (d, J=12.2 Hz, 2H), 2.65 (t, J=11.3 Hz, 2H), 2.14 (s, 3H), 1.72 (d, J=11.4 Hz, 2H), 1.46-1.61 (m, 1H), 1.39 (q, J=6.6 Hz, 2H), 1.25 (qd, J=12.0, 3.4 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. filtrationThe resultant solid was filtered
  3. customair dried
  4. dissolutiondissolved in DCM
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered

Sources & evidence

ORD record
ord-b38277de5f9f466db8c6bd7e0bb2b96b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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