Hydrazine, ethyl-, ethanedioate (1:1) → 4-(5-benzyl-1-ethyl-(1H-pyrazol-3-yl))-1-t-butoxycarbonylpiperidine

HRID 860175Notes

Reaction equation

HRID 860175 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[CH2:15][C:16](=O)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C(O)=O.[CH2:32]([NH:34][NH2:35])[CH3:33]>CO>[CH2:17]([C:16]1[N:34]([CH2:32][CH3:33])[N:35]=[C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:15]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 96181Hydrazine, ethyl-, ethanedioate (1:1)HCID 18187492Tert-butyl 4-(3-oxo-4-phenylbutanoyl)piperidine-1-carboxylate

Product 1

HCID 181875724-(5-benzyl-1-ethyl-(1H-pyrazol-3-yl))-1-t-butoxycarbonylpiperidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

1-(1-t-Butoxycarbonylpiperidin-4-yl)-4-phenylbutane-1,3-dione (from Step A, either Method A or Method B), (0.851 g, 2.46 mmol) in methanol (25 mL) was added over 10 min to a suspension of ethylhydrazine oxalate (0.444 g, 2.96 mmol) in methanol (5 mL) in a 60° C. oil bath. After 15 h, the reaction was concentrated in vacuo and the residue was purified by repeated FC using a gradient of 50–100% ethyl acetate in hexanes to give first 4-(5-benzyl-1-ethyl-(1H-pyrazol-3-yl))-1-t-butoxycarbonylpiperidine as the higher Rf product isomer and then the title compound as the lower Rf. 1H NMR (500 MHz): δ 7.26˜7.31 (m, 4H), 7.19˜7.23 (m, 1H), 5.72 (s, 1H), 4.16˜4.24 (m, 2H), 4.08 (q, J=7.3 Hz, 2H), 3.94 (s, 2H), 2.76˜2.82 (m, 2H), 2.66 (tt, J=3.6 & 11.9 Hz, 1H), 1.80˜1.85 (m, 2H), 1.49˜1.58 (m, 2H), 1.48 (s, 9H), 1.45 (t, J=7.3 Hz, 3H); ESI-MS 370.2 (M+H), HPLC A: 3.70 min. The other isomer's ESI-MS 370.2 (M+H), HPLC A: 3.77 min.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customthe residue was purified

Sources & evidence

ORD record
ord-398f5a60244d437ab8c15de1c87f81cd
Source dataset
uspto-grants-2006_12
Patent number
US07153868B2

Reaction notes

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