Ammonium formate → Tert-butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylate

HRID 415074Notes

Reaction equation

HRID 415074 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N+:22]([O-])=O)[O:5][CH:6]1[CH2:11][CH2:10][N:9](C(OCCCC)=O)[CH2:8][CH2:7]1.[CH:25]([O-:27])=[O:26].[NH4+].[C:29]1([CH3:35])[CH:34]=CC=C[CH:30]=1.O>[Fe]>[NH2:22][C:21]1[CH:20]=[CH:19][C:4]([O:5][CH:6]2[CH2:7][CH2:8][N:9]([C:25]([O:27][C:29]([CH3:35])([CH3:34])[CH3:30])=[O:26])[CH2:10][CH2:11]2)=[CH:3][C:2]=1[Cl:1]

Participants

5

Reactant 3

HCID 2723923Ammonium formateHCID 22272177Toluene waterHCID 86642029Butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate

Product 1

HCID 59349578Tert-butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Procedure

tert-Butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylate was prepared in the same manner as tert-Butyl 4-(3-(4-amino-5-chloro-2 methylphenoxy)propyl)piperazine-1-carboxylate. Reaction of N-Boc-4-hydroxypiperidine with sodium hydride in anhydrous THF, followed by 2-chloro-4-fluoro-1-nitrobenzene (commercially available from Acros) gave tert-butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate. Reduction of the tent-butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate using ammonium formate and iron dust in refluxing toluene-water mixture gave tert-butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylate in 79% yield. 1H-NMR (400 MHz, CDCl3): δ 6.88 (m, 1H), 6.70 (m, 2H), 4.26 (m, 1H), 3.79 (s, br, 2H), 3.68 (m, 2H), 3.30 (m, 2H), 1.86 (m, 2H), 1.71 (m, 2H), 1.56 (s, 9H). MS (EI): 227 (MH+).

Sources & evidence

ORD record
ord-c8bde9176d6c4aec8520b0f3982594ce
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Reaction notes

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