1-Propanol → (R)-tert-butyl 3-(5-cyanopyridin-2-ylamino)pyrrolidine-1-carboxylate

HRID 72122

Reaction equation

[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.F[C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][N:16]=1.CCN(C(C)C)C(C)C.C(O)CC>CCOC(C)=O>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([NH:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[N:16][CH:17]=1)#[N:22]

Participants

Conditions

Temperature: 150 °C

Procedure

A heavy-walled, screw-cap glass tube was charged with (R)-tert-butyl 3-aminopyrrolidine-1-carboxylate (3.30 g, 17.7 mmol), 2-fluoro-5-cyanopyridine (1.63 g, 13.2 mmol), i-Pr2NEt (6.3 mL, 35.5 mmol) and n-PrOH (3 mL). The mixture was heated at 150° C. in an oil bath for 2 h. The mixture was diluted with EtOAc (180 mL), washed with 1% aq HCl (3×40 mL), satd aq NaHCO3 (40 mL) and brine (40 mL), and dried over Na2SO4. Removal of the solvent left an oil (3.28 g) which was purified by chromatography on a 40-g silica gel cartridge eluted with a 0-100% EtOAc in hexanes gradient to afford (R)-tert-butyl 3-(5-cyanopyridin-2-ylamino)pyrrolidine-1-carboxylate (3.41 g, 88% based on 2-fluoro-5-cyanopyridine). LC-MS Method 1 tR=1.57 min, m/z=289.

Workup

customA heavy-walled, screw-cap glass tube
washwashed with 1% aq HCl (3×40 mL)
dry with materialdried over Na2SO4
customRemoval of the solvent
waitleft an oil (3.28 g) which
customwas purified by chromatography on a 40-g silica gel cartridge
washeluted with a 0-100% EtOAc in hexanes gradient

Sources & evidence

ORD record: ord-7ee7d64f5f4e4e9aa1ddbbf045262891
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08828985B2

Linked notes

Loading…