Hydrochloric Acid → 4-[(1S)-1-[[5-chloro-2-(3-fluorophenoxy)pyridine-3-carbonyl]amino]ethyl]benzoic Acid

HRID 1293191Notes

Reaction equation

HRID 1293191 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:16]([NH:18][C@H:19]([C:21]2[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=2)[CH3:20])=[O:17])[C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)=[N:6][CH:7]=1.[OH-].[Na+].Cl>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:16]([NH:18][C@H:19]([C:21]2[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:29][CH:30]=2)[CH3:20])=[O:17])[C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69415945Methyl 4-[(1S)-1-({[5-chloro-2-(3-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate

Product 1

HCID 115777924-[(1S)-1-[[5-chloro-2-(3-fluorophenoxy)pyridine-3-carbonyl]amino]ethyl]benzoic AcidYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of methyl 4-[(1S)-1-({[5-chloro-2-(3-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate (step 2, 180 mg, 0.42 mmol) in tetrahydrofuran (3 mL) was added 2 N sodium hydroxide aqueous The reaction mixture was stirred at 65° C. for 5 h. After cooling, the reaction mixture was acidified by the addition of 2 N hydrochloric acid (2 mL). The aqueous mixture was partitioned between water (50 mL) and dichloromethane (50 mL) and the organic phase was separated. The aqueous phase was extracted with dichloromethane (50 mL). The combined organic layer was washed with brine (100 mL), dried (sodium sulfate), and concentrated. The residual solids were recrystallized from ethyl acetate to afford 103 mg (60%) of the title compound as white solids: 1H-NMR (CDCl3) δ 8.56 (1H, d, J=3.0 Hz), 8.16 (1H, d, J=3.0 Hz), 8.08–8.05 (3H, m), 7.47–7.40 (3H, m), 7.07–6.91 (3H, m), 5.43–5.33 (1H, m), 1.60 (3H, d, J=7.1 Hz), a peak of COOH was not observed; MS (ESI) m/z 415 (M+H)+, 413 (M−H)−.

Workup

  1. temperatureAfter cooling
  2. customThe aqueous mixture was partitioned between water (50 mL) and dichloromethane (50 mL)
  3. customthe organic phase was separated
  4. extractionThe aqueous phase was extracted with dichloromethane (50 mL)
  5. washThe combined organic layer was washed with brine (100 mL)
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residual solids were recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-325d4feb7f4a48b0809ddb5bb8bccf41
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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