Methanol → 4-Hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester

To a suspension of 4-hydroxyamino-1-methoxy-piperidine-4-carboxylic acid (1.0 g, 5.26 mmol) in methanol (25 ml) at 0-10° C. was added thionyl chloride (1.14 ml, 1.88 g, 15.77 mmol) and the reaction mixture was heated at reflux for 48 hours. After cooling, the mixture was concentrated, the residue diluted with ice water (20 ml) and neutralised with aqueous sodium bicarbonate. The aqueous phase was extracted with diethyl ether (3×25 ml), the combined organic layers washed with aqueous sodium bicarbonate and brine, dried over sodium sulfate and concentrated. Yield: 0.53 g of 4-hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester (title compound P4ii.2) as a viscous, yellowish oil. This material was identical to the compound described above under preparation ‘EXAMPLE 11, Step 3’.

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 48 hours
3. temperatureAfter cooling
4. concentrationthe mixture was concentrated
5. additionthe residue diluted with ice water (20 ml)
6. extractionThe aqueous phase was extracted with diethyl ether (3×25 ml)
7. washthe combined organic layers washed with aqueous sodium bicarbonate and brine
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customdescribed above under preparation ‘EXAMPLE 11, Step 3’

ORD record

ord-c412afc450e244a89538b18655c3584a

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018135B2