Diethyl Malonate → 7-Benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

HRID 902524Notes

Reaction equation

[C:1]([O:9]CC)(=O)[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[CH2:14]([N:21]1[C:26]2[S:27][CH:28]=[CH:29][C:25]=2[C:24](=O)[O:23]C1=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C=O)C>[CH2:6]([O:5][C:3]([C:2]1[C:1](=[O:9])[N:21]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:26]2[S:27][CH:28]=[CH:29][C:25]=2[C:24]=1[OH:23])=[O:4])[CH3:7]

Participants

Conditions

Temperature: 0 °C

Procedure

Diethyl malonate (2.14 mL, 0.014 mol) was added slowly to a suspension of sodium hydride (60% dispersion in mineral oil, 0.66 g, 0.017 mol) in 50 mL anhydrous DMF stirred at 0° C. under argon. The solution was stirred for 15 minutes. Solid 1-benzyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (58) (3.58 g, 0.014 mol) was added, and the solution was heated at 110° C. for 2 hours. The solvent was then removed under vacuum, and the residue was dissolved in water and washed with ethyl acetate. The aqueous layer was acidified with dil. HCl to precipitate the product, which was collected by vacuum filtration to give 3.09 g (68%) of 7-benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyrdine-5-carboxylic acid ethyl ester. MP 146° C. 1H-NMR (DMSO-d6) δ 1.30 (t, J=7.2 Hz, 3H), 4.32 (q, J=7.2 Hz, 2H), 5.25 (s, 2H), 7.24-7.36 (m, 7H), 13.21 (b, 1H) ppm; EIMS m/z 330 (M+1).

Workup

stirringThe solution was stirred for 15 minutes
temperaturethe solution was heated at 110° C. for 2 hours
customThe solvent was then removed under vacuum
dissolutionthe residue was dissolved in water
washwashed with ethyl acetate
customto precipitate the product, which
filtrationwas collected by vacuum filtration

Sources & evidence

ORD record: ord-e2d9e9928e1840f3bbb0d68afd50e744
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07365200B2

Reaction notes

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