Sodium hydride → Ethyl 6,7-dihydro-4-hydroxy-7-isobutyl-6-oxothieno[2,3-b]pyridine-5-carboxylate

HRID 1013878Notes

Reaction equation

HRID 1013878 reaction equation
[CH2:1]([N:5]1[C:10]2[S:11][CH:12]=[CH:13][C:9]=2[C:8](=[O:14])O[C:6]1=[O:15])[CH:2]([CH3:4])[CH3:3].C([C:18](CC)([C:22]([O-:24])=[O:23])C([O-])=O)C.[H-].[Na+].CN(C)[C:31](=O)[CH3:32]>>[OH:14][C:8]1[C:9]2[CH:13]=[CH:12][S:11][C:10]=2[N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[C:6](=[O:15])[C:18]=1[C:22]([O:24][CH2:31][CH3:32])=[O:23]

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 69515632,2-DiethylpropanedioateHCID 866016361-isobutyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione

Product 1

HCID 67316158Ethyl 6,7-dihydro-4-hydroxy-7-isobutyl-6-oxothieno[2,3-b]pyridine-5-carboxylateYield 74%

Conditions

Temperature
110 °C

Procedure

To a solution of crude 1-isobutyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (2.0 g) in N,N-dimethylacetamide (30 mL) were added diethylmalonate (2.13 g, 13.3 mmol) and sodium hydride (0.32 g, 13.3 mmol). The resulting mixture was heated at 110° C. for 4 h, cooled to room temperature, concentrated to dryness and dissolved in water. This aqueous solution was washed with ethyl acetate, acidified with concentrated hydrochloric acid and followed by extraction with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated. The residue was purified on a silica gel flash chromatography column eluted with 10% ethyl acetate-hexane to afford the title compound as a slightly yellow oil (1.95 g, 74% yield for Steps C and D combined). 1H NMR (400 MHz, CDCl3): δ 7.32 (d, 1H), 6.90 (d, 1H), 4.49 (q, 2H), 3.90 (d, 2H), 2.49 (m, 1H), 1.46 (t, 3H), 0.98 (d, 6H); MS: m/e 296 (M+H+).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated to dryness
  3. dissolutiondissolved in water
  4. washThis aqueous solution was washed with ethyl acetate
  5. extractionfollowed by extraction with dichloromethane
  6. dry with materialThe extract was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified on a silica gel flash chromatography column
  9. washeluted with 10% ethyl acetate-hexane

Sources & evidence

ORD record
ord-0b10c47f0a37401b883d865023c5fb02
Source dataset
uspto-grants-2011_07
Patent number
US07982040B2

Reaction notes

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