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

HRID 2066705Notes

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-1a0ad6c66af349909d23a782396978ff
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293746B2

Reaction notes

Loading…