Morpholine → 3-Chloro-5-morpholinoaniline

HRID 1431399Notes

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>C1COCC1.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

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 (0.19 g, 0.39 mmol), Pd2dba3 (0.177 g, 0.19 mmol) and morpholine (0.464 g, 5.33 mmol) in THF (9.70 mL). To this mixture was added LHMDS in THF (19.37 mL, 19.37 mmol) and the resulting reaction was heated to 65° C. Stirring continued for 2.5 h. After which 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

customthe resulting reaction
temperatureAfter which the 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-ac7c885202dd4856937a9807305b07e9
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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