Sodium Hydroxide → 2-[4-(2-Cyclopropylmethylsulfanyl-pyridin-3-ylmethoxy)-3,5-difluoro-phenyl]-cyclopropane carboxylic acid

HRID 63001Notes

Reaction equation

HRID 63001 reaction equation
C[O:2][C:3]([CH:5]1[CH2:7][CH:6]1[C:8]1[CH:13]=[C:12]([F:14])[C:11]([O:15][CH2:16][C:17]2[C:18]([S:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)=[N:19][CH:20]=[CH:21][CH:22]=2)=[C:10]([F:28])[CH:9]=1)=[O:4].[OH-].[Na+]>C1COCC1.CO>[CH:25]1([CH2:24][S:23][C:18]2[C:17]([CH2:16][O:15][C:11]3[C:12]([F:14])=[CH:13][C:8]([CH:6]4[CH2:7][CH:5]4[C:3]([OH:4])=[O:2])=[CH:9][C:10]=3[F:28])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:27][CH2:26]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 90118307HCID 90118307, compound

Product 1

HCID 742226172-[4-(2-Cyclopropylmethylsulfanyl-pyridin-3-ylmethoxy)-3,5-difluoro-phenyl]-cyclopropane carboxylic acidYield 98.9%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

After 2-[4-(2-cyclopropylmethylsulfanyl-pyridin-3-ylmethoxy)-3,5-difluoro-phenyl]-cyclopropane carboxylic acid methyl ester (13 mg, 0.031 mmol) obtained in Step A was dissolved in THF/MeOH (1 mL/1 mL), 10N sodium hydroxide solution (30 mg, 0.31 mmol) was added thereto, and the mixture was stirred at room temperature for 12 hours. After the termination of the reaction, the reactant was concentrated under reduced pressure, and the residue was diluted with water. The aqueous layer was added with 1N HCl to adjust the pH to 2˜3, and then extracted with EtOAc. The organic layer was dried with MgSO4, concentrated under reduced pressure, and purified by column chromatography (eluent, MeOH/DCM=5/95) to obtain the title compound (12 mg, 97%).

Workup

  1. customAfter the termination of the reaction
  2. concentrationthe reactant was concentrated under reduced pressure
  3. additionthe residue was diluted with water
  4. additionThe aqueous layer was added with 1N HCl
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried with MgSO4
  7. concentrationconcentrated under reduced pressure
  8. custompurified by column chromatography (eluent, MeOH/DCM=5/95)

Sources & evidence

ORD record
ord-06f34d2096d3432ab75b290046c51e49
Source dataset
uspto-grants-2016_09
Patent number
US09447044B2

Reaction notes

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