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

HRID 1360524Notes

Reaction equation

HRID 1360524 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-32681d34bb154cb0be828ddf30e67052
Source dataset
uspto-grants-2011_02
Patent number
US07879849B2

Reaction notes

Loading…