Cesium carbonate → 3-(1-Hydroxyethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one
Reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[O:4][C:3]=1[CH:13]([OH:15])[CH3:14].CC1(C)C(C)(C)OB([C:24]2[S:28][C:27]([CH2:29][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:15][CH:13]([C:3]1[O:4][C:5](=[O:12])[C:6]2[C:11]([C:2]=1[C:24]1[S:28][C:27]([CH2:29][N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[CH:26][CH:25]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:14]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
The title compound was made in a similar way as that of the intermediate B1, using 4-bromo-3-(1-hydroxyethyl)-1H-isochromen-1-one (Intermediate A2, 0.4 g, 1.49 mmol), 4-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)methyl)morpholine (0.598 g, 1.93 mmol), Pd(PPh3)4 (0.086 g, 0.074 mmol) and Cs2CO3 (0.678 g, 2.1 mmol). The crude was purified via reverse phase chromatography with a Biotage C18 SNAP 60 g column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%); Phase B ACN 99.9%, formic acid 0.1%) to afford the title compound (0.26 g, 48%).
Workup
- customThe crude was purified via reverse phase chromatography with a Biotage C18 SNAP 60 g column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%)
Sources & evidence
- ORD record
- ord-5846ba0c1a234495850de2f79081e260
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09321776B2
Reaction notes
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