Water → Phenylmethyl 4-{1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-1-piperazinecarboxylate

HRID 419435Notes

Reaction equation

HRID 419435 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].C([O-])([O-])=O.[K+].[K+].FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:34]1[CH2:39][CH2:38][CH:37]([N:40]2[CH2:45][CH2:44][N:43]([C:46]([O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:47])[CH2:42][CH2:41]2)[CH2:36][CH2:35]1.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:34]1[CH2:39][CH2:38][CH:37]([N:40]2[CH2:41][CH2:42][N:43]([C:46]([O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:47])[CH2:44][CH2:45]2)[CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 184681411-Fluoro-5-methoxy-2-methyl-4-nitrobenzeneHCID 86625193Phenylmethyl 4-(4-piperidinyl)-1-piperazinecarboxylate bis(trifluoroacetate) salt

Product 1

HCID 59452952Phenylmethyl 4-{1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-1-piperazinecarboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

5-Fluoro-4-methyl-2-nitrophenyl methyl ether (2.76 g, 14.9 mmol) was dissolved in DMSO (50 mL), and K2CO3 (10.3 g, 74.5 mmol) and phenylmethyl 4-(4-piperidinyl)-1-piperazinecarboxylate bis(trifluoroacetate) salt (Example 112, step B) (8.0 g, 15 mmol) were added. Reaction was stirred overnight. Poured into H2O and extracted (2×) with EtOAc. Combined organic layers were back-extracted (5×) with H2O and then dried over MgSO4, filtered, concentrated on to silica gel and flash chromatographed to give the title compound of step C (4.6 g, 66%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.72 (s, 1H), 7.03-7.46 (m, 5H), 6.64 (s, 1H), 5.03 (s, 2H), 3.85 (s, 3H), 3.06-3.59 (m, 6H), 2.67 (t, J=11.5 Hz, 2H), 2.26-2.57 (m, 5H), 2.15 (s, 3H), 1.81 (d, J=11.5 Hz, 2H), 1.36-1.68 (m, 2H).

Workup

  1. customReaction
  2. extractionextracted (2×) with EtOAc
  3. extractionCombined organic layers were back-extracted (5×) with H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated on to silica gel and flash
  7. customchromatographed

Sources & evidence

ORD record
ord-c7faefb670e74b6c9e032c4c44576cfe
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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