Sodium Hydroxide → 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid

HRID 2392052Notes

Reaction equation

HRID 2392052 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8]([O:10]C)=[O:9])=[CH:5][C:4]=1[C:12]1[N:16]([CH3:17])[N:15]=[CH:14][CH:13]=1)[CH3:2].[Cl:18]N1C(=O)CCC1=O.[OH-].[Na+]>O1CCCC1>[Cl:18][C:13]1[CH:14]=[N:15][N:16]([CH3:17])[C:12]=1[C:4]1[CH:5]=[C:6]([C:8]([OH:10])=[O:9])[S:7][C:3]=1[CH2:1][CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 31398ChlorosuccinimideHCID 57826625methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

Product 1

HCID 578268684-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acidYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (300 mg, 1.2 mmol) [Prepared in Example 98] and N-chlorosuccinimide (160 mg, 1.2 mmol) in tetrahydrofuran (6 ml) was stirred in a sealed tube for 1 h at 70° C. 6N sodium hydroxide (1 ml, 5.99 mmol) was added in one portion and the solution stirred an additional 1 h. The reaction mixture was then partitioned between H2O-DCM and the pH of the aqueous phase was adjusted to 4 and washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated then purified via column chromatography (silica, 20% EtOAC in hexanes) yielding 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid (325 mg, 1.20 mmol, 100% yield) as a yellow oil: LCMS (ES) m/e 271, 273 (M, M+2)+.

Workup

  1. customThe reaction mixture was then partitioned between H2O-DCM
  2. washwashed several times with DCM
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. concentrationconcentrated
  5. customthen purified via column chromatography (silica, 20% EtOAC in hexanes)

Sources & evidence

ORD record
ord-b2b10ff86bd34538b5701684d1a39245
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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