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

HRID 1961090Notes

Reaction equation

HRID 1961090 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]([O:9]C)=[O:8])=[CH:4][C:3]=1[C:11]1[N:15]([CH3:16])[N:14]=[CH:13][CH:12]=1.[Cl:17]N1C(=O)CCC1=O.[OH-].[Na+]>O1CCCC1>[Cl:17][C:12]1[CH:13]=[N:14][N:15]([CH3:16])[C:11]=1[C:3]1[CH:4]=[C:5]([C:7]([OH:9])=[O:8])[S:6][C:2]=1[CH3:1]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 31398ChlorosuccinimideHCID 57826485methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

Product 1

HCID 578263804-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acidYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (2.75 g, 11.64 mmol) [Prepared in Example 99] and N-chlorosuccinimide (1.55 g, 11.64 mmol) in tetrahydrofuran (58 ml) was stirred in a sealed tube for 1 h at 70° C. Sodium hydroxide (9.70 ml, 58 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-methyl-2-thiophenecarboxylic acid (2.3 g, 8.96 mmol, 77% yield) as a yellow oil: LCMS (ES) m/e 257, 259 (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-f3e14e1a335a4d789ef3880b9ffa4734
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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