Acetic Acid → tert-Butyl (3-hydroxypropyl)methylcarbamate

482.5 ml (5 eq) acetic acid dissolved in 386 ml water were added dropwise over a period of 45 min to a solution of 95.6 g (1 eq) tert-butyl 3-(tert-butyldimethylsilyloxy)propyl(methyl)-carbamate dissolved in 386 ml THF at 0° C. and the reaction mixture was then stirred for 20 h at room temperature. As the starting product had not yet been completely converted, the mixture was cooled to 0° C., 50 ml dilute acetic acid were added over a period of 20 min and the mixture was stirred for a further 1 h at 0° C. The reaction course was monitored by thin-layer chromatography (10% EtOAc/hexane). Once the conversion was almost complete, the reaction mixture was concentrated under reduced pressure, adjusted to a pH of ˜9 with Na2CO3 solution and extracted with 10% IPA/CH3Cl. The combined organic phases were dried over Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (silica gel; 10% EtOAc/hexane). 40 g (66%) of product were obtained in the form of a colourless oil.

1. temperaturethe mixture was cooled to 0° C.
2. stirringthe mixture was stirred for a further 1 h at 0° C
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. extractionextracted with 10% IPA/CH3Cl
5. dry with materialThe combined organic phases were dried over Na2SO4
6. customremoval of the solvent under reduced pressure
7. customthe residue was purified by column chromatography (silica gel; 10% EtOAc/hexane)

ORD record

ord-a6b14fdcea2f41ed84f907d86f7ae83f

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206156B2