Tetrahydrofuran → 4-(4-Chlorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylic acid

HRID 734667Notes

Reaction equation

[Cl: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.C1COCC1.[OH-].[Na+]>CO.O>[Cl: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 (735 mg, 2.63 mmol, 1.00 equiv) was dissolved in 3/1 MeOH:THF (12 mL total). Following addition of 2.5N NaOH (3 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 494 mg (71%) of the acid as an off-white solid. MS (ES+) m/e 266 [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
dry with materialNaCl, dried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated en vacuo
customazeotroped several times with hexanes

Sources & evidence

ORD record: ord-447b958a032d4bc6bf7cee889e795264
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592357B2

Reaction notes

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