Sodium Hydroxide → 4-(4-Fluorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylic acid

HRID 734661Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]([O:18]C)=[O:17])=[CH:4][CH:3]=1.[OH-].[Na+]>CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]([OH:18])=[O:17])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

The product from Step 1 (0.200 g, 0.76 mmol, 1.00 equiv) was dissolved in MeOH (3 mL). Following addition of 2.5N NaOH (1 mL), the reaction mixture was heated to 60° C. for 6 hours, then stirred at room temperature for an additional 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed again with 1N NaOH. The aqueous phases were combined and acidified to pH˜1 with 5N HCl, and extracted twice with ethyl acetate. The combined organic extracts were washed with satd NaCl, dried over Na2SO4, and filtered. The filtrate was concentrated en vacuo and azeotroped several times with hexanes to afford 128 mg (67%) of the acid as an off-white solid. MS (ES+) m/e 250 [M+H]+.

Workup

extractionextracted with ethyl acetate
washThe organic phase was washed again with 1N NaOH
extractionextracted twice with ethyl acetate
washThe combined organic extracts were washed with satd NaCl
dry with materialdried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated en vacuo
customazeotroped several times with hexanes

Sources & evidence

ORD record: ord-a098cd68ba7e4ae3b6731e7fd81e4299
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592357B2

Reaction notes

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