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Lithium hydroxide, monohydrate → 6-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid

HRID 872947
Notes
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Reaction equation

HRID 872947 reaction equation
C[O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.O.[OH-].[Li+]>C1COCC1.O.CO.Cl>[F:24][C:21]1[CH:20]=[CH:19][C:18]([C:13]2[C:12]([CH2:11][O:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:25])=[O:2])=[CH:5][N:6]=3)=[C:16]([CH3:17])[O:15][N:14]=2)=[CH:23][CH:22]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 684447416-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 684418986-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acidYield 79.8%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidCatalystHCID 887
Methanol
Catalyst
HCID 887MethanolSolvent
HCID 962WaterSolvent
HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (1.4 g, 4.2 mmol) (538 mg, 1.1 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (94 mg, 2.2 mmol) in water (5 mL) and methanol (1 mL) added and the resulting mixture stirred at room temperature overnight. The mixture was acidified to pH 4 with HCl (25%, 3 drops) and methanol (2 drops) added. A gum began to form and the mixture was cooled at 0° C. for 1.5 h and then the aqueous layer decanted off. Trituration with diethylether and hexane afforded the title compound (1.1 g, 78%) which was obtained as a white solid. MS: m/e=327.3 [M−H]−.

Workup

  1. additionadded
  2. additionadded
  3. customto form
  4. temperaturethe mixture was cooled at 0° C. for 1.5 h
  5. customthe aqueous layer decanted off

Sources & evidence

ORD record
ord-8e4609e9978844cd9d1fafe1b6118fbe
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08975397B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes