Lithium Hydroxide → 5-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acid

HRID 2074082Notes

Reaction equation

HRID 2074082 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([O:15]C)=[O:14])[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[CH:8]=2)=[CH:4][CH:3]=1.C1COCC1.[Li+].[OH-]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([OH:15])=[O:14])[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[CH:8]=2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 68360279methyl [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetate

Product 1

HCID 670925255-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acidYield 93.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 12 liter, three-neck, round bottom flask equipped with mechanical stirrer was charged with Methyl [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetate (235 g, 0.72 mol), THF (3.5 L), methanol (1.2 L), and 2 M LiOH (1.2 L). The resulting solution was stirred at room temperature for 1.5 hours. After LC-MS showed the absence of starting material, the majority of the THF was removed by rotary evaporation. The solution was then acidified with 2 M HCl (pH=3) and the white precipitate was filtered and washed with water. After being dried under reduced pressure, 210 g (93%) of the title compound was obtained. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.53 (d, 2 H), 7.68 (d, 2 H), 7.31 (t, 2 H), 7.14 (t, 2 H), 6.57 (s, 1 H), 5.00 (s, 2 H), 4.01 (s, 2 H); m/z (APCI+) for C17H14N3O2F 312.2 (M+H)+.

Workup

  1. customA 12 liter, three-neck, round bottom flask equipped with mechanical stirrer
  2. customthe majority of the THF was removed by rotary evaporation
  3. filtrationthe white precipitate was filtered
  4. washwashed with water
  5. customAfter being dried under reduced pressure

Sources & evidence

ORD record
ord-3a90672e12ef4b9ea8c3606f09635cb8
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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