Ammonium Chloride → 5-ethyl-7-oxo-6,7-dihydro-5H-thieno[3,2-b]pyridine-4,6-dicarboxylic acid 6-ethyl ester 4-isopropyl ester

HRID 2378097Notes

Reaction equation

HRID 2378097 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:10](=[O:18])[C:9]2[S:19][CH:20]=[CH:21][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[CH2:22]([Mg]Br)[CH3:23].[Cl-].[NH4+]>C1COCC1.[Cu]I>[CH:1]([O:4][C:5]([N:7]1[CH:12]([CH2:22][CH3:23])[CH:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:10](=[O:18])[C:9]2[S:19][CH:20]=[CH:21][C:8]1=2)=[O:6])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 589267297-oxo-7H-thieno[3,2-b]pyridine-4,6-dicarboxylic acid 6-ethyl ester 4-isopropyl esterHCID 178418443HCID 178418443, compound2×

Product 1

HCID 589267135-ethyl-7-oxo-6,7-dihydro-5H-thieno[3,2-b]pyridine-4,6-dicarboxylic acid 6-ethyl ester 4-isopropyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Mix 7-oxo-7H-thieno[3,2-b]pyridine-4,6-dicarboxylic acid 6-ethyl ester 4-isopropyl ester (0.512 g, 1.66 mmol) and copper(I) iodide (0.695 g, 3.65 mmol) in THF (35 ml). Cool the mixture to −78° C. Inject ethyl magnesium bromide (3.0 M in diethyl ether, 1.66 ml) and stir for 1.5 h. Add another portion of ethyl magnesium bromide (3.0 M in diethyl ether, 3.30 ml) and keep the reaction at −78° C. for one more hour. Warm up to −20° C. overnight in a freezer. Pour the reaction mixture into saturated ammonium chloride solution (200 ml). Extract with ethyl acetate (3×200 ml). Combine all the organic layers, dry over Na2SO4, filter and concentrate to give 5-ethyl-7-oxo-6,7-dihydro-5H-thieno[3,2-b]pyridine-4,6-dicarboxylic acid 6-ethyl ester 4-isopropyl ester (0.520 g, 93%) as a crude oil. MS (ES+): 340 (M+H).

Workup

  1. customthe reaction at −78° C. for one more hour
  2. temperatureWarm up to −20° C. overnight in a freezer
  3. extractionExtract with ethyl acetate (3×200 ml)
  4. dry with materialCombine all the organic layers, dry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-3011f7357f964093943f1b8c07c62605
Source dataset
uspto-grants-2008_12
Patent number
US07470705B2

Reaction notes

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