Morpholine → 3,3,7-Trimethyl-6-morpholinoindolin-2-one

HRID 1618612Notes

Reaction equation

Br[C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([C:6]([CH3:14])([CH3:13])[C:7](=[O:12])[NH:8]2)=[CH:4][CH:3]=1.CC([O-])(C)C.[Na+].[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:13][C:6]1([CH3:14])[C:5]2[C:9](=[C:10]([CH3:11])[C:2]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:3][CH:4]=2)[NH:8][C:7]1=[O:12]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 6-bromo-3,3,7-trimethylindolin-2-one (0.63 g, 2.44 mmol), NaOt-Bu (0.33 g, 3.42 mmol), Pd2(dba)3 (0.11 g, 0.12 mmol), morpholine (0.51 mL, 5.86 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.11 mL, 0.29 mmol) in Toluene (2.5 mL) was flushed with N2 for 10 minutes and then heated in a microwave at 120° C. for 80 minutes. The mixture was cooled to rt and concentrated. Purification of the residue by flash chromatography over silica gel, using 40% EtOAc in hexane, gave 3,3,7-trimethyl-6-morpholinoindolin-2-one. 1H-NMR (DMSO-d6) δ 10.27 (1H, s), 7.04 (1H, d, J=8.0 Hz), 6.64 (1H, d, J=8.0 Hz), 3.72 (4H, s), 2.78 (4H, s), 2.13 (3H, s), 1.21 (6H, s). Mass Spectrum (ESI) m/e=261.1 (M+1).

Workup

customwas flushed with N2 for 10 minutes
temperatureThe mixture was cooled to rt
concentrationconcentrated
customPurification of the residue by flash chromatography over silica gel

Sources & evidence

ORD record: ord-d58ea449f1e14887a52268522dfd09cd
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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