Ammonium Chloride → tert-butyl (3S,4S)-4-(4-amino-2-chlorophenoxy)-3-fluoropiperidine-1-carboxylate

HRID 633422Notes

Reaction equation

[Cl:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C@H:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][C@@H:6]1[F:18].[NH4+].[Cl-]>CCO.O.CCOC(C)=O.[Fe]>[NH2:23][C:21]1[CH:20]=[CH:19][C:3]([O:4][C@H:5]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[CH2:7][C@@H:6]2[F:18])=[C:2]([Cl:1])[CH:22]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of tert-butyl (3S,4S)-4-(2-chloro-4-nitrophenoxy)-3-fluoropiperidine-1-carboxylate (0.8 g, 1.0 eq, 2.2 mmol), Fe (0.6 g, 5.0 eq, 10.8 mmol) and NH4Cl (0.6 g, 5.0 eq, 10.8 mmol) in EtOH/H2O (1:1, 50 mL) was stirred at 90° C. for 1 hour. The mixture was cooled to room temperature and concentrated under reduced pressure to leave a crude solid. The crude mixture was dissolved in EtOAc (50 mL) and partitioned with H2O (50 mL). Organic layers were separated and the aqueous layer was washed with EtOAc (50 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum to give the desired product in 45% yield. This product was taken to next step with out further purification.

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated under reduced pressure
customto leave a crude solid
custompartitioned with H2O (50 mL)
customOrganic layers were separated
washthe aqueous layer was washed with EtOAc (50 mL)
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-1902c28a453d4b70bd690f74c441e576
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321763B2

Reaction notes

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