N,N,N-Tributylbutan-1-aminium fluoride--hydrogen fluoride (1/1/2) → Tert-butyl 4-[(benzyloxy)methyl]-3-fluoro-4-hydroxypiperidine-1-carboxylate

HRID 70789Notes

Reaction equation

[F:1][H-]F.[K+].CCCC[N+](CCCC)(CCCC)CCCC.F.F.[F-].[CH2:25]([O:32][CH2:33][C:34]12[O:40][CH:39]1[CH2:38][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36][CH2:35]2)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(Cl)(Cl)Cl>[CH2:25]([O:32][CH2:33][C:34]1([OH:40])[CH2:35][CH2:36][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38][CH:39]1[F:1])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Potassium bifluoride (1.22 g) and tetrabutylammonium dihydrogentrifluoride (472 mg) were added to tert-butyl 6-[(benzyloxy) methyl]-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (2.50 g), followed by heating and stirring at 120° C. for 2 days. The reaction was diluted with chloroform and filtered through Celite. The residue obtained by concentration of the solvent under reduced pressure was purified by silica gel column chromatography (EtOAc/hexane) to obtain tert-butyl 4-[(benzyloxy)methyl]-3-fluoro-4-hydroxypiperidine-1-carboxylate (1.76 g).

Workup

temperatureby heating
filtrationfiltered through Celite
customThe residue obtained by concentration of the solvent under reduced pressure
customwas purified by silica gel column chromatography (EtOAc/hexane)

Sources & evidence

ORD record: ord-50961c977c3c40c8a5ece1e330f477df
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822688B2

Reaction notes

Loading…