Hydrochloric Acid → 3-Ethylthiophene-2-carboxylic acid

HRID 583915Notes

Reaction equation

O.NN.[OH-].[K+].C([C:9]1[S:13][C:12]([C:14]([OH:16])=[O:15])=[CH:11][CH:10]=1)(=O)C.Cl.[CH2:18](O)[CH2:19]OCCO>O>[CH2:18]([C:11]1[CH:10]=[CH:9][S:13][C:12]=1[C:14]([OH:16])=[O:15])[CH3:19]

Participants

Conditions

Temperature: 110 °C

Procedure

Hydrazine monohydrate (0.97 mL, 1.019 mol) and potassium hydroxide (1.12 g, 20 mmol) were added to a solution of 5-acetyl-thiophene-2-carboxylic acid (1.70 g, 10 mmol) in diethylene glycol (20 mL) and water (1 mL). The reaction mixture was stirred in an oil bath at 110° C. for 16 hrs, cooled to rt, acidified with 2N HCl and then extracted with methylene chloride (4×50 mL). Organic layers were combined, dried, concentrated and subjected to chromatography separation on silica gel (eluted with 10% methanol/methylene chloride) to produce 3-ethylthiophene-2-carboxylic acid Compound 3A as a pale yellow solid (1.161 g, 74%). 1H NMR (300 MHz, CD3OD) δ 7.59 (d, J 3.7, 1H), 6.87 (d, J 3.7, 1H), 2.88 (q, J 7.5, 1H), 1.32 (t, J 7.5, 3H); MS (ESI) m/z: 155 (M−H+). Using the procedure of Example 1, Compound 1E was acylated with Compound 3A mediated by DIC/HOBt in anhydrous DMF to produce Compound 32 (59% yield). 1H NMR (300 MHz, (CD3)2CO) δ 8.90 (s, br, 1H), 8.25 (d, 1H), 7.88 (q, 4H), 7.45 (s, br, 2H), 7.10 (d, 1H) 6.45 (s, br, 2H), 3.05 (q, 2H), 1.42 (t, 3H); MS (ESI) m/z: 393 (M+H+), 415 (M+Na+).

Workup

temperaturecooled to rt
extractionextracted with methylene chloride (4×50 mL)
customdried
concentrationconcentrated
customsubjected to chromatography separation on silica gel (eluted with 10% methanol/methylene chloride)

Sources & evidence

ORD record: ord-37f0b99fd46a49e88ca908e331b249ca
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06924302B2

Reaction notes

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