Diethyl Ether → HCID 22462243, compound

HRID 1936568Notes

Reaction equation

HRID 1936568 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26](OC2C=CC([N+]([O-])=O)=CC=2)=[O:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].CCOCC>CN(C)C=O>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][N:23]([C:26]([N:1]2[CH2:2][CH2:3][CH:4]([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)[CH2:5][CH2:6]2)=[O:27])[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 11395974-(4-Piperidyl)pyridineHCID 22462238HCID 22462238, compound

Product 1

HCID 22462243HCID 22462243, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

4-(4-Pyridyl)piperidine (2.44 g) was added to a stirred suspension of 1-t-butoxycarbonyl-4-(4-nitrophenoxycarbonyl)piperazine (5.26 g) in dimethylformamide (90 mL) at 25° C. The reaction mixture was heated at 105° C. for 18 hours. The dimethylformamide was evaporated and water (500 mL) added, The aqueous phase was extracted with ethyl acetate. The organic phase was washed with 1M sodium hydroxide solution (5×100 mL) and saturated brine (2×100 mL), dried and evaporated, The residue was purified by chromatography on silica gel using a mixture of dichloromethane: methanol: 0.88 ammonia (94:5:1) as eluent to give a yellow oil. Trituration with ether gave, as a pale yellow solid, 1-t-butoxycarbonyl-4-[4-(4-pyridyl)-1-piperidylcarbonyl]piperazine (2.62 g); mp 143-4° C.; NMR (CDCl3) 1.44(s, 9H), 1.58-1.78(m, 2H), 1.78-1.92(d, 2H), 2.60-2.75(m, 1H), 2.80-2.96 (m, 2H), 3.92-3.25(t, 4H), 3.38-3.50(m, 4H), 3.82(d, 2H), 7.10(d, 2H), 8.51(d, 2H); EI-MS m/z 375(M+H).

Workup

  1. customThe dimethylformamide was evaporated
  2. additionwater (500 mL) added
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washThe organic phase was washed with 1M sodium hydroxide solution (5×100 mL) and saturated brine (2×100 mL)
  5. customdried
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel using
  8. additiona mixture of dichloromethane
  9. custommethanol: 0.88 ammonia (94:5:1) as eluent to give a yellow oil

Sources & evidence

ORD record
ord-ed85c3c99fba40298fb9f4366ad51e30
Source dataset
uspto-grants-2002_05
Patent number
US06391880B1

Reaction notes

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