Naphthalene → tert-Butyl N-(2-amino-1-methylcyclopentyl)carbamate

A mixture of lithium granules (7.17 g, 1195 mmol) and naphthalene (57.39 g, 448.36 mmol) in dry dimethoxyethane (1900 ml) was stirred at room temperature for 2 hours. The deep blue solution was then cooled to 0° C. and a solution of tert-butyl N-[1-methyl-2-(4-methylbenzenesulfonamido)cyclopentyl]carbamate (55.0 g, 149.45 mmol) in dry dimethoxyethane (300 ml) was added drop wise over 30 minutes. The mixture was stirred at 0° C. for 3 hours. The un-dissolved lithium was removed by filtration and 1M HCl solution (aq, 720 ml) was added to the filtrate. The organic layer was washed with further 1M HCl (aq, 2×600 ml). The combined aqueous layers were washed with diethyl ether (2×600), and then basified with 2M NaOH (aq) to give pH 12-14. The aqueous layer was then extracted with ethyl acetate (5×600 ml). The combined organics were dried over sodium sulfate and then concentrated in vacuo. This was then purified by column chromatography (silica, 0-4% methanol/DCM) to afford the title compound.

1. temperatureThe deep blue solution was then cooled to 0° C.
2. stirringThe mixture was stirred at 0° C. for 3 hours
3. customThe un-dissolved lithium was removed by filtration and 1M HCl solution (aq, 720 ml)
4. additionwas added to the filtrate
5. washThe organic layer was washed with further 1M HCl (aq, 2×600 ml)
6. washThe combined aqueous layers were washed with diethyl ether (2×600)
7. customto give pH 12-14
8. extractionThe aqueous layer was then extracted with ethyl acetate (5×600 ml)
9. dry with materialThe combined organics were dried over sodium sulfate
10. concentrationconcentrated in vacuo
11. customThis was then purified by column chromatography (silica, 0-4% methanol/DCM)

ORD record

ord-8fbc0323bf7f4380af944681acead54b

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156829B2