Ammonium Chloride → Ethyl 5-amino-4-methoxythiophene-2-carboxylate

Temperature

50 °C

A mixture of ethyl 4-methoxy-5-nitrothiophene-2-carboxylate (Int. 68) (300 mg, 1.297 mmol) (prepared as described in Step 4 hereabove reported), and ammonium chloride (139 mg, 2.59 mmol) in EtOH/water=2/1 (18 ml) was heated at 50° C. until complete dissolution. Iron powder (435 mg, 7.78 mmol) was added, and the reaction was heated at 80° C. for 2 hours. The mixture was filtered and the filtrate was concentrated under vacuum; the residue was portioned between brine and EtOAc and the organic phase was dried over sodium sulfate. The solvent was removed to afford ethyl 5-amino-4-methoxythiophene-2-carboxylate (Int. 69) in a mixture with approximately 30% of corresponding methyl ester (261 mg, 1.297 mmol, MS/ESI+201.9 [MH]+). This intermediate was used as such in the following step.

1. temperaturethe reaction was heated at 80° C. for 2 hours
2. filtrationThe mixture was filtered
3. concentrationthe filtrate was concentrated under vacuum
4. dry with materialthe organic phase was dried over sodium sulfate
5. customThe solvent was removed

ORD record

ord-1f953e59a22b4bf3927beb31b17e41b5

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440954B2