Lithium Hydroxide → 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylic acid

HRID 2283847Notes

Reaction equation

HRID 2283847 reaction equation
[OH-].[Li+].[C:3]([O:7][C:8]([NH:10][C:11]([CH3:28])([CH3:27])[CH2:12][C:13]1[N:17]([CH2:18][CH2:19][O:20][CH3:21])[N:16]=[C:15]([C:22]([O:24]CC)=[O:23])[CH:14]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO.O>[C:3]([O:7][C:8]([NH:10][C:11]([CH3:28])([CH3:27])[CH2:12][C:13]1[N:17]([CH2:18][CH2:19][O:20][CH3:21])[N:16]=[C:15]([C:22]([OH:24])=[O:23])[CH:14]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 66958319ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate

Product 1

HCID 669586825-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylic acidYield 37.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Lithium hydroxide (17.1 g, 407 mmol) was added to a solution of ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate (37.6 g, 102 mmol) in methanol (141 mL) and water (47 mL). The reaction mixture was stirred for 2 days and then most of the methanol was removed under reduced pressure. The aqueous residue was cooled in an ice bath and then combined with 1 N hydrochloric acid (350 mL) and tert-butyl methyl ether. The layers were separated. The volume of the organic layer was reduced under vacuum and then diluted with hexanes. A precipitate was isolated by filtration, washed with water, and suction dried to provide 13.09 g of 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylic acid as a white solid. The aqueous layer was extracted with chloroform while maintaining the pH of the aqueous layer at pH 4-5 by the addition of 1 N hydrochloric acid. The chloroform extracts were combined, dried over sodium sulfate and magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in tert-butyl methyl ether, diluted with hexanes, and then concentrated under reduced pressure. A white solid was isolated by filtration, washed with hexanes, and suction dried to provide an additional 21.8 g of product.

Workup

  1. custommost of the methanol was removed under reduced pressure
  2. temperatureThe aqueous residue was cooled in an ice bath
  3. customThe layers were separated
  4. additiondiluted with hexanes
  5. customA precipitate was isolated by filtration
  6. washwashed with water, and suction
  7. customdried

Sources & evidence

ORD record
ord-babac5a4e57a41baa96cce16e1b3cb3a
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

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