Hydrochloric Acid → 4'-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid

HRID 967119Notes

Reaction equation

HRID 967119 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19]([C:21]3[C:22]([O:27][C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)=[N:23][CH:24]=[CH:25][CH:26]=3)=[O:20])=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[OH-].[Na+].Cl.CO.ClCCl>C(O)(C)(C)C.O>[F:34][C:31]1[CH:32]=[CH:33][C:28]([O:27][C:22]2[C:21]([C:19]([NH:18][CH2:17][C:14]3[CH:15]=[CH:16][C:11]([C:7]4[CH:8]=[CH:9][CH:10]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=4)=[CH:12][CH:13]=3)=[O:20])=[CH:26][CH:25]=[CH:24][N:23]=2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 206014024'-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid methyl esterHCID 21226129Dichloromethane methanol

Product 1

HCID 99550014'-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acidYield 51.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolvent

Procedure

A mixture of 300 mg (0.66 mmol.) 4′-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid methyl ester and 1.6 mL 1.0 N NaOH in 10 mL t-butanol and 3 mL water and refluxed for 4 hours. The mixture was poured into water, acidified to pH 1 with 2N HCl, then extracted with ethyl acetate. The ethyl acetate extracted were combined, washed successively with water, brine then dried (MgSO4) and concentrated to give an oil. Chromatography on Silica Gel eluting with methanol/dichloromethane (1:40) yielded a foam. Recrystallization from ethyl acetate/hexanes afforded 151 mg 4′-[[[2-[4-Fluorophenoxy]-pyridine-3-carbonyl]-amino]-methyl]-biphenyl-3-carboxylic acid as a solid, mp 184-6° C.

Workup

  1. temperaturerefluxed for 4 hours
  2. extractionextracted with ethyl acetate
  3. extractionThe ethyl acetate extracted
  4. washwashed successively with water, brine
  5. dry with materialthen dried (MgSO4)
  6. concentrationconcentrated
  7. customto give an oil
  8. customRecrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-49f7f71d18c343e790fc43aada383e0f
Source dataset
uspto-grants-2005_10
Patent number
US06953810B2

Reaction notes

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