Morpholine → 3-Chloro-5-morpholinoaniline
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:9])[CH:8]=1)[NH2:5].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:9][C:7]1[CH:6]=[C:4]([CH:3]=[C:2]([N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)[CH:8]=1)[NH2:5]Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 65 °C
Procedure
To a stirred solution of 3-bromo-5-chloroaniline (1.00 g, 4.84 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.185 g, 0.39 mmol), Pd2dba3 (0.177 g, 0.194 mmol) and morpholine (0.464 g, 5.33 mmol) in tetrahydrofuran (9.7 mL) was added LHMDS in THF (19.37 mL, 19.37 mmol). The resulting mixture was heated to 65° C. and stirring continued for 2.3 h. The reaction was cooled to rt and then poured into water (100 mL) and extracted with EtOAc (2×150 mL) and DCM (2×150 mL). The combined organic layers were dried over magnesium sulfate and the crude product was purified on silica gel (0 to 100% DCM in EtOAc) to give 3-chloro-5-morpholinoaniline. Mass Spectrum (ESI) m/e=213.1 (M+1).
Workup
- temperatureThe reaction was cooled to rt
- extractionextracted with EtOAc (2×150 mL) and DCM (2×150 mL)
- dry with materialThe combined organic layers were dried over magnesium sulfate
- customthe crude product was purified on silica gel (0 to 100% DCM in EtOAc)
Sources & evidence
- ORD record
- ord-d898171310af477fa35c16ed968f3eb7
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08940724B2
Reaction notes
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