Potassium Hydroxide → 6-Chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid

HRID 1943950Notes

Reaction equation

HRID 1943950 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([O:10]CC2C=CC=CC=2)=[O:9])=[C:6]([F:18])[C:5]([N:19](S(CCCOC2C=CC(OC)=CC=2)(=O)=O)[S:20]([CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)(=[O:22])=[O:21])=[CH:4][CH:3]=1.[OH-].[K+]>CO>[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([F:18])[C:5]([NH:19][S:20]([CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)(=[O:22])=[O:21])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 131730287benzyl 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)-N-(3-(4-methoxyphenoxy)propylsulfonyl)propylsulfonamido)benzoate

Product 1

HCID 670890016-Chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 100 mL, round-bottomed flask was charged with benzyl 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)-N-(3-(4-methoxyphenoxy)propylsulfonyl)propylsulfonamido)benzoate (1.08 g, 1.47 mmol), potassium hydroxide (4.40 mL, 4.40 mmol) and MeOH (10 mL). The reaction mixture was stirred at room temperature until TLC showed that the starting material had been consumed (about 12 hours). HCl (5 mL, 1N) was added. Then the reaction mixture was partitioned between EtOAc (500 mL) and water (100 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×200 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield crude 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid. The crude product was purified by silica gel chromatography (EtOAc/hexane from 1/4 to 1/0, v/v) to afford 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid (0.58 g, 95.1%). 1H NMR (400 MHz, CDCl3) δ 10.02 (s, 1H), 7.39-7.53 (m, 2H), 6.81 (m, 4H), 4.01 (t, 2H), 3.64 (s, 3H), 3.34 (t, 2H), 2.11 (m, 2H).

Workup

  1. customhad been consumed (about 12 hours)
  2. additionHCl (5 mL, 1N) was added
  3. customThen the reaction mixture was partitioned between EtOAc (500 mL) and water (100 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×200 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4b80d592b4bb4442adf889a6f3c7877a
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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