Ethanol → tert-Butyl [(3S,5R)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate

HRID 1499507Notes

Reaction equation

[N+:1]([C:4]1[C:5]([N:13]2[CH2:18][C@H:17]([C:19]([F:22])([F:21])[F:20])[CH2:16][C@H:15]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:14]2)=[C:6]2[CH2:12][CH2:11][O:10][C:7]2=[N:8][CH:9]=1)([O-])=O.[Cl-].[NH4+].CCO>[Fe].O>[NH2:1][C:4]1[C:5]([N:13]2[CH2:18][C@H:17]([C:19]([F:22])([F:20])[F:21])[CH2:16][C@H:15]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:14]2)=[C:6]2[CH2:12][CH2:11][O:10][C:7]2=[N:8][CH:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of tert-butyl [(3S,5R)-1-(5-nitro-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (227.1 mg, 0.5252 mmol), iron powder (289.6 mg, 5.186 mmol) and ammonium chloride (462.4 mg, 8.644 mmol) was added EtOH (5.0 mL) followed by water (2.5 mL). The mixture was stirred at 80° C. for 1 h. The reaction mixture was filtered through a pad of diatomaceous earth. The diatomaceous earth pad was eluted with a 10% aqueous solution of K3PO4 (50 mL), and EtOAc (50 mL). The separated organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated to give the crude sub-title compound (211.5 mg). The crude product was used directly in the next step without further purification. LCMS calc. for C18H26F3N4O3 (M+H)+: m/z=403.2. found 403.2.

Workup

filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
washThe diatomaceous earth pad was eluted with a 10% aqueous solution of K3PO4 (50 mL), and EtOAc (50 mL)
washThe separated organic layer was washed with brine (50 mL)
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-e507af0df978425da03de9f85dcdc679
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200004B2

Reaction notes

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