Cesium carbonate → 3-(1-Hydroxyethyl)-4-(4-(2-morpholinoethoxy)phenyl)-1H-isochromen-1-one

HRID 634362

Reaction equation

HRID 634362 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[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]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[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[CH:26][CH:25]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:14]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 46259104-(2-Morpholin-4-ylethoxy)benzeneboronic acid, pinacol esterHCID 1181312554-Bromo-3-(1-hydroxyethyl)-1H-isochromen-1-one2×

Product 1

HCID 1181313013-(1-Hydroxyethyl)-4-(4-(2-morpholinoethoxy)phenyl)-1H-isochromen-1-oneYield 33.5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

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, 0.36 g, 1.35 mmol), 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)-morpholine (0.45 g, 1.35 mmol), Pd(PPh3)4 (0.078 g, 0.068 mmol) and Cs2CO3 (0.53 g, 1.6 mmol). The crude was filtered, diluted with 1M HClaqueous (3 ml) and purified via reverse phase chromatography with a Biotage C18 SNAP 120 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 (0.179 g, 33%).

Workup

  1. filtrationThe crude was filtered
  2. additiondiluted with 1M HClaqueous (3 ml)
  3. custompurified via reverse phase chromatography with a Biotage C18 SNAP 120 g column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%)

Sources & evidence

ORD record
ord-afa818dd489e4ba094a373f5f0c4aa08
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Linked notes

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