Carbamide Peroxide → 4-((1-(tert-butoxycarbonyl)-4-carbamoylpiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid

HRID 880909Notes

Reaction equation

HRID 880909 reaction equation
[C:1]([N:5]1[CH:9]=[C:8]([CH2:10][C:11]2([C:24]#[N:25])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[C:7]([C:26]([O:28]CC)=[O:27])=[N:6]1)([CH3:4])([CH3:3])[CH3:2].NC(N)=[O:33].OO>CO.[OH-].[Na+]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C:11]([CH2:10][C:8]2[C:7]([C:26]([OH:28])=[O:27])=[N:6][N:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:9]=2)([C:24](=[O:33])[NH2:25])[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

5

Reactant 2

HCID 31294Carbamide PeroxideHCID 67491622tert-butyl 4-((1-tert-butyl-3-(ethoxycarbonyl)-1H-pyrazol-4-yl)methyl)-4-cyanopiperidine-1-carboxylate

Product 1

HCID 674914864-((1-(tert-butoxycarbonyl)-4-carbamoylpiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acidYield 93.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a 0° C. solution of tert-butyl 4-((1-tert-butyl-3-(ethoxycarbonyl)-1H-pyrazol-4-yl)methyl)-4-cyanopiperidine-1-carboxylate (455 mg, 1.09 mmol) in methanol (11 mL) was added a solution of urea-hydrogen peroxide (1.05 g, 10.9 mmol) in 1 M aqueous sodium hydroxide (10.9 mL), dropwise. After stirring for 18 hours at room temperature, volatiles were removed under reduced pressure and the resultant slurry was taken up in water (50 mL), acidified with 2 N aqueous hydrochloric acid and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated to yield 4-((1-(tert-butoxycarbonyl)-4-carbamoylpiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid (418 mg) as a colorless solid. −APCI (M−H) 407.3; 1H NMR (400 MHz, DMSO-d6, δ): 12.33 (br. s., 1H), 7.47 (s, 1H), 7.11 (br. s., 1H), 6.99 (s, 1H), 3.59 (d, J=13.3 Hz, 2H), 2.89 (s, 2H), 2.77 (m, 2H), 1.84 (m, 2H), 1.44 (s, 9H), 1.31 (s, 9H), 1.16 (m, 2H).

Workup

  1. customvolatiles were removed under reduced pressure
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d5c6150c86ef42f3a009a38c5e3ef90a
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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