Hydrochloric Acid → 1-tert-butoxycarbonylmethyl-1H-pyrazole-3,5-dicarboxylic acid 3-ethyl ester

HRID 31528Notes

Reaction equation

HRID 31528 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[N:7]=1)=[O:5])[CH3:2].[Li+].[OH-].Cl>O1CCCC1.O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([OH:13])=[O:12])[N:8]([CH2:16][C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[N:7]=1)=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([CH2:16][C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 586466791-tert-butoxycarbonylmethyl-1H-pyrazole-3,5-dicarboxylic acid diethyl ester

Product 2

HCID 586466791-tert-butoxycarbonylmethyl-1H-pyrazole-3,5-dicarboxylic acid diethyl esterHCID 586467061-tert-butoxycarbonylmethyl-1H-pyrazole-3,5-dicarboxylic acid 3-ethyl esterYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

According to a related procedure (Lee, H. H.; Cain, B. F.; Denny, W. A.; Buckleton, J. S.; Clark, G. R. J. Org. Chem. 1989, 54, 428-431) a solution of 9.6 g (29.4 mmol) of pyrazole triester (2) in 250 mL of tetrahydrofuran and 50 mL of water was cooled to −10° C. and 30 mL (30 mmol) of a chilled 1M LiOH solution was added dropwise. The reaction mixture was slowly allowed to warm to 0° C., then was stirred at 0° C. for an additional hour. The mixture was then diluted with 600 mL of ethyl acetate and acidified to pH=1 with 1 N HCl solution. The organic extract was washed with brine, dried over sodium sulfate, and evaporated to a residue which was chromatographed on silica gel (1% methanol in dichloromethane, followed by 90:9:1 dichloromethane:methanol:acetic acid) to give 4.66 g (53%) of desired 1-tert-butoxycarbonylmethyl-1H-pyrazole-3,5-dicarboxylic acid 3-ethyl ester L3), as well as 2.3 g of recovered starting triester (2). 1H NMR of 3 (300 MHz, CDCl3) δ 7.49 (s, 1H), 5.28 (s, 2H), 4.42 (q, J=7.1 Hz), 1.45 (s, 9 H), 1.40 (t, J=7.2 Hz, 3H).

Workup

  1. extractionThe organic extract
  2. washwas washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated to a residue which
  5. customwas chromatographed on silica gel (1% methanol in dichloromethane, followed by 90:9:1 dichloromethane:methanol:acetic acid)

Sources & evidence

ORD record
ord-f4d27f8cd4b64bb28d403aea7d8b7e15
Source dataset
uspto-grants-2008_09
Patent number
US07425640B2

Reaction notes

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