Hydrochloric Acid → 5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid

HRID 391241Notes

Reaction equation

HRID 391241 reaction equation
C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[F:18])[C:7]([O:19][CH3:20])=[CH:6][C:5]=1[F:21].[OH-].[Na+].O.Cl>CN1CCCC1=O>[Cl:17][C:13]1[C:12]([F:18])=[C:11]([CH:16]=[CH:15][CH:14]=1)[CH2:10][C:8]1[C:7]([O:19][CH3:20])=[CH:6][C:5]([F:21])=[C:4]([CH:9]=1)[C:3]([OH:22])=[O:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 575728695-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid methyl ester

Product 1

HCID 575728415-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acidYield 93.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid methyl ester (100 g) obtained in Example 2, Step III was dissolved in 1-methyl-2-pyrrolidinone (500 ml), and 2.5% V/W aqueous alkali solution prepared from 8N-aqueous sodium hydroxide solution (54.7 ml) and water (192.6 ml) was added dropwise with stirring at room temperature. After the dropwise addition, the mixture was stirred for 3.5 hr, and acidified by dropwise addition of 2N-hydrochloric acid (240 ml) with stirring at room temperature. The precipitated crystals were stirred for 2 hr and collected by filtration. The filtrate was washed with 50% methanol aqueous solution (100 ml) and dried at an outer temperature of 70° C. to give 5-(3-chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoic acid (89.4 g, yield 93.4%).

Workup

  1. additionwas added dropwise
  2. additionAfter the dropwise addition
  3. stirringthe mixture was stirred for 3.5 hr
  4. stirringwith stirring at room temperature
  5. stirringThe precipitated crystals were stirred for 2 hr
  6. filtrationcollected by filtration
  7. washThe filtrate was washed with 50% methanol aqueous solution (100 ml)
  8. customdried at an outer temperature of 70° C.

Sources & evidence

ORD record
ord-642d02038d2e4fdfba34fa531f47154f
Source dataset
uspto-grants-2013_02
Patent number
US08383819B2

Reaction notes

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