Morpholine → 4-(3-Iodo-5-nitrophenyl)morpholine
Reaction equation
F[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([I:11])[CH:3]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>CS(C)=O>[I:11][C:4]1[CH:3]=[C:2]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 130 °C
Procedure
To a solution of 1-fluoro-3-iodo-5-nitrobenzene (4.0 g, 15 mmol) in DMSO (7.5 mL) was added morpholine (3.26 mL, 37.5 mmol), and the mixture (which instantly became purple) was heated to 130° C. for 30 min in the microwave. Purification was attempted by directly loading the mixture onto a CombiFlash column (80 g; load neat w/CH2Cl2 rinse; 100:0 to 60:40 hexanes:EtOAc over 35 minutes) but the mixture crashed at the top of the column and not all the mixture could be loaded. Nonetheless, after an inital spike in pressure, purification was possible, and the residual material was purified in a second purification (24 g; load w/CH2Cl2; 100:0 to 60:40 hexanes:EtOAc over 20 minutes). Concentration of the combined fractions from the two purifications provided 4-(3-iodo-5-nitrophenyl)morpholine (4.01 g, 12.0 mmol, 80%) as a bright yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H); 7.67 (s, 1H); 7.47 (s, 1H); 3.89 (s, 4H); 3.26 (s, 4H).
Workup
- customPurification
- washonto a CombiFlash column (80 g; load neat w/CH2Cl2 rinse; 100:0 to 60:40 hexanes:EtOAc over 35 minutes)
- customNonetheless, after an inital spike in pressure, purification
- customthe residual material was purified in a second purification (24 g; load w/CH2Cl2; 100:0 to 60:40 hexanes:EtOAc over 20 minutes)
Sources & evidence
- ORD record
- ord-88b54eb143764aec8ea1d320f3de7c9a
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735417B2
Reaction notes
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