2-Fluoro-4-nitrophenol → 1-[2-(2-Fluoro-4-nitrophenoxy)ethyl]pyrrolidine

HRID 409675Notes

Reaction equation

Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[F:10][C:11]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=1[OH:20].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.O>[F:10][C:11]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=1[O:20][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

1-(2-Chloro-ethyl)-pyrrolidine hydrochloride (1.2 g, 7.0 mmol, 1.1 equiv) is added to a suspension of 2-fluoro-4-nitrophenol (1 g, 6.4 mmol) and cesium carbonate (5.2 g, 15.9 mmol, 2.5 equiv) in DMF (20 mL). The resulting mixture is heated to 80° C. and stirred for 18 h. Additional 1-(2-chloro-ethyl)-pyrrolidine hydrochloride (1 g) is added and the mixture is stirred for 3 h at 80° C. The reaction mixture is cooled to RT, diluted with EtOAc and H2O. The layers are separated and the aqueous layer is extracted with EtOAc. The organic phase is washed with H2O, dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5) to provide the title compound as a yellow solid. ESI-MS: 255.1 [MH]+; tR=2.57 min (system 1); TLC: Rf=0.55 (DCM/MeOH+1% NH3aq, 95:5).

Workup

stirringthe mixture is stirred for 3 h at 80° C
temperatureThe reaction mixture is cooled to RT
customThe layers are separated
extractionthe aqueous layer is extracted with EtOAc
washThe organic phase is washed with H2O
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue is purified by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5)

Sources & evidence

ORD record: ord-b49b29c0bd664e96a6649bafb1055bae
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759517B2

Reaction notes

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