Tetrahydrofuran → 2-Methyl-4-(2-naphthalenyl)-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylic acid

HRID 734658Notes

Reaction equation

[CH3:1][C:2]1[NH:3][C:4](=[O:22])[CH2:5][CH:6]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=2)[C:7]=1[C:8]([O:10]C)=[O:9].C1COCC1.[OH-].[Na+]>CO.O>[CH3:1][C:2]1[NH:3][C:4](=[O:22])[CH2:5][CH:6]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=2)[C:7]=1[C:8]([OH:10])=[O:9]

Participants

Conditions

Temperature: 60 °C

Procedure

The product from Step 1 (2.32 g, 7.9 mmol, 1.00 equiv) was dissolved in MeOH (32 mL). THF (10 mL) was added, followed by 2.5N NaOH (10 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. The aqueous solution was 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 hexane. The resulting solid was triturated with 50% CH2Cl2/hexanes to afford 570 mg of the acid as an off-white solid. MS (ES+) m/e 282 [M+H]+.

Workup

extractionextracted with ethyl acetate
washThe organic phase was washed again with 1N NaOH
extractionThe aqueous solution was extracted 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 hexane
customThe resulting solid was triturated with 50% CH2Cl2/hexanes

Sources & evidence

ORD record: ord-0c1d5e1ebf124aee8cf209bc6f78edc5
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592357B2

Reaction notes

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