Cesium carbonate → Tert-butyl 4-((4-amino-3-nitrophenoxy)methyl)piperidine-1-carboxylate

HRID 415100Notes

Reaction equation

HRID 415100 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16].S(O[CH2:29][CH:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1)(C1C=CC(C)=CC=1)(=O)=O>CC(N(C)C)=O>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[CH2:32][CH2:31]2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 37588824-Amino-3-NitrophenolHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidine

Product 1

HCID 59349493Tert-butyl 4-((4-amino-3-nitrophenoxy)methyl)piperidine-1-carboxylateYield 54.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

Cesium carbonate (16.29 g, 50 mmoles, 2 equivalents) was added to a stirred solution of 4-amino-3-nitrophenol (3.85 g, 25 mmoles, 1 equivalent) and tert-butyl 4-(tosyloxymethyl)piperidine-1-carboxylate (10.16 g, 27.5 mmoles, 1.1 equivalent) in anhydrous DMA (25 mls). The stirred reaction mixture was then heated to 90° C. (thermostatically controlled heating mantle) for 22 hours. The reaction mixture was then allowed to cool to room temperature and was filtered through a plug of Celite. The reaction flask and the Celite were then washed with ethyl acetate (250 ml). The organic solution was then transferred to a separatory funnel and extracted with additional ethyl acetate (3×200 ml). The combined ethyl acetate solution was then washed with water (2×100 ml), saturated sodium chloride (2×100 ml), dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. This material was triturated with diethylether to give a crystalline solid which was filtered off, washed with ether to give 4.76 g of tert-butyl 4-((4-amino-3-nitrophenoxy)methyl)piperidine-1-carboxylate (yield=54%). 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 7.89 (d, 1H), 7.74 (d, 1H), 3.82 (d, 2H), 3.65 (m, 2H), 2.40 (s, 3H), 1.76 (m, 1H), 1.54 (m, 2H), 1.38 (s, 9H), 0.98 (m, 2H). MS (EI): 352 (MH+).

Workup

  1. customThe stirred reaction mixture
  2. temperaturethermostatically controlled heating mantle) for 22 hours
  3. temperatureto cool to room temperature
  4. filtrationwas filtered through a plug of Celite
  5. washThe reaction flask and the Celite were then washed with ethyl acetate (250 ml)
  6. customThe organic solution was then transferred to a separatory funnel
  7. extractionextracted with additional ethyl acetate (3×200 ml)
  8. washThe combined ethyl acetate solution was then washed with water (2×100 ml), saturated sodium chloride (2×100 ml)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThis material was triturated with diethylether
  13. customto give a crystalline solid which
  14. filtrationwas filtered off
  15. washwashed with ether

Sources & evidence

ORD record
ord-91c1ca937b1d47dc8b9af40faa705061
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Reaction notes

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