Triethylamine → tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate

HRID 537098Notes

Reaction equation

HRID 537098 reaction equation
[Br:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1(C(O)=O)[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:34])C=CC=CC=1.C([N:46]([CH2:49]C)CC)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1([N:46]=[C:49]=[O:34])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 674917184-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

Product 1

HCID 71507904tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylateYield 111.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (2.54 g, 5.9 mmol), diphenylphosphoryl azide (1.79 g, 6.5 mmol) and triethylamine (0.91 mL, 6.5 mmol) in toluene (15 mL) was heated at reflux for 3 hours. The mixture was then cooled to room temperature and the solvent removed in vacuo. The crude product was purified by column chromatography to give tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (2.8 g, 100%). 1H NMR (300 MHz, CDCl3, δ): 7.47 (s, 1H), 4.68 (m, 1H), 3.99 (m, 2H), 2.95 (m, 2H), 2.67 (s, 2H), 1.62 (m, 4H), 1.45 (m, 15H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. customthe solvent removed in vacuo
  4. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-bb78be9be6614c22a110d1ed4fbdd28b
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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