Morpholine → 3,3-Dimethyl-6-morpholinoindoline
Reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:12])([CH3:11])[CH2:7][NH:8]2)=[CH:4][CH:3]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>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>[CH3:11][C:6]1([CH3:12])[C:5]2[C:9](=[CH:10][C:2]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:3][CH:4]=2)[NH:8][CH2:7]1Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 65 °C
Procedure
The 6-iodo-3,3-dimethylindoline (250 mg, 0.915 mmol), morpholine (0.399 mL, 4.58 mmol), Pd2(dba)3 (33.5 mg, 0.037 mmol), and 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (34.9 mg, 0.073 mmol) were dissolved in THF (2.0 mL) and 1M lithium bis(trimethylsilyl)amide (5.03 mL, 5.03 mmol) solution in THF was added to a sealed tube and heated to 65° C. for 1 h. The reaction was cooled to rt and then poured into water (30 mL) and extracted with EtOAc (1×150 mL) and DCM (1×150 mL). The combined organic layers were dried over magnesium sulfate and the crude product was purified by medium pressure chromatography (silica, 50 to 100% EtOAc:DCM) to give 4-(3,3-dimethylindolin-6-yl)morpholine. Mass Spectrum (ESI) m/e=233.2 (M+1).
Workup
- temperatureThe reaction was cooled to rt
- extractionextracted with EtOAc (1×150 mL) and DCM (1×150 mL)
- dry with materialThe combined organic layers were dried over magnesium sulfate
- customthe crude product was purified by medium pressure chromatography (silica, 50 to 100% EtOAc:DCM)
Sources & evidence
- ORD record
- ord-c06e71bfd1b440db85602899b96bb1c7
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765940B2
Reaction notes
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