Triphenylphosphine → tert-butyl 4-(4-nitro-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1045918Notes

Reaction equation

HRID 1045918 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[N+:15]([C:18]1[CH:19]=[N:20][NH:21][CH:22]=1)([O-:17])=[O:16].O[CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCCC(C)C.CCOC(C)=O>[N+:15]([C:18]1[CH:19]=[N:20][N:21]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:22]=1)([O-:17])=[O:16]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 163764-nitro-1H-pyrazoleHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 56777238tert-butyl 4-(4-nitro-1H-pyrazol-1-yl)piperidine-1-carboxylateYield 92.3%

Reagents, catalysts & solvents 3

HCID 78922-MethylpentaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

DIAD (3.92 mL, 19.90 mmol) was added dropwise to a stirred solution of 4-nitro-1H-pyrazole (1.5 g, 13.27 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (2.67 g, 13.27 mmol) and triphenylphosphine (5.22 g, 19.90 mmol) in THF (30 mL) cooled to 0° C. under a nitrogen atmosphere. The resulting solution was stirred at 0° C. for 10 minutes then allowed to warm to room temperature and stirred overnight. The mixture was diluted with isohexane (80 mL) and EtOAc (20 mL) and then stirred vigorously. The mixture was filtered and the solid washed with isohexane (20 mL). The combined filtrates were evaporated and the residue was purified by chromatography on silica, eluting with a gradient of 20-50% EtOAc in isohexane. Fractions containing product were combined and evaporated to afford tert-butyl 4-(4-nitropyrazol-1-yl)piperidine-1-carboxylate (3.63 g, 92% yield); 1H NMR spectrum: (300 MHz, DMSO) 1.42 (9H, s), 1.79-1.84 (2H, m), 2.01-2.05 (2H, m), 2.87-2.98 (2H, m), 4.40-4.47 (1H, m), 8.28 (1H, s), 8.95 (1H, s). b) A mixture of tert-butyl 4-(4-nitropyrazol-1-yl)piperidine-1-carboxylate (3.63 g, 12.25 mmol) and 10% palladium on carbon (0.326 g, 0.31 mmol) in EtOH (200 mL) were stirred under an atmosphere of hydrogen for 18 hours. The mixture was filtered through Celite and the filtrate loaded onto an SCX column. The mixture was eluted first with MeOH and then with a 7M solution of NH3 in MeOH. Fractions containing product were combined and evaporated to afford tert-butyl 4-(4-aminopyrazol-1-yl)piperidine-1-carboxylate (2.100 g, 64% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 1.41 (9H, s), 1.65-1.74 (2H, m), 1.89-1.92 (2H, m), 2.81-2.93 (2H, m), 3.75 (2H, s), 3.99 (2H, d), 4.09-4.16 (1H, m), 6.91 (1H, s), 7.06 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=211.0.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. stirringstirred vigorously
  4. filtrationThe mixture was filtered
  5. washthe solid washed with isohexane (20 mL)
  6. customThe combined filtrates were evaporated
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a gradient of 20-50% EtOAc in isohexane
  9. additionFractions containing product
  10. customevaporated

Sources & evidence

ORD record
ord-d43c4b9b6f74418a859fd0d8d232078c
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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