Potassium Carbonate → 4-(2-(3-Nitro-5-(trifluoromethyl)phenoxy)ethyl)morpholine

HRID 1050166Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.[O:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][OH:23])[CH2:17][CH2:16]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N+:12]([C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1)[O:23][CH2:22][CH2:21][N:18]1[CH2:19][CH2:20][O:15][CH2:16][CH2:17]1)([O-:14])=[O:13]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 1-fluoro-3-nitro-5-(trifluoromethyl)benzene (800 mg, 3.83 mmol), 2-morpholinoethanol (552 mg, 4.21 mmol) and K2CO3 (1586 mg, 11.48 mmol) in DMF (20 mL) was stirred at 90° C. for 10 h. The mixture was concentrated. To the residue was added DCM (150 mL) and the mixture was stirred for 10 min and then filtered. The filtrate was concentrated. The residue was purified by silica column chromatography (PE/EA=10:1˜5:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.6) were combined and concentrated to yield a yellow solid of 4-(2-(3-nitro-5-(trifluoromethyl)phenoxy)ethyl)morpholine (600 mg, 1.780 mmol, 46.5% yield): 1H NMR (400 MHz, CDCl3): δ 8.02 (s, 1H), 7.87 (s, 1H), 7.43 (s, 1H), 4.16 (t, J=5.6 Hz, 2H), 3.72-3.63 (m, 4H), 2.79 (t, J=5.6 Hz, 2H), 2.58-2.47 (m, 4H). ES-LCMS m/z: 321 (M+H).

Workup

concentrationThe mixture was concentrated
additionTo the residue was added DCM (150 mL)
stirringthe mixture was stirred for 10 min
filtrationfiltered
concentrationThe filtrate was concentrated
customThe residue was purified by silica column chromatography (PE/EA=10:1˜5:1)
concentrationconcentrated

Sources & evidence

ORD record: ord-9c84ebf0fbb24dd0aeb408bfcffb05a8
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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