Cesium fluoride → 4'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-2,3',5'-trimethylbiphenyl-4-carboxylic acid

HRID 2243549Notes

Reaction equation

HRID 2243549 reaction equation
[CH3:1][C:2]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[C:19]([CH3:32])[C:3]=1[O:4][CH2:5][CH2:6][NH:7][C@@H:8]([CH3:18])[C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[OH:10].Br[C:34]1[CH:42]=[CH:41][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=1[CH3:43].[F-].[Cs+].O1CCOCC1>O1CCCC1.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.O.C(O)C>[OH:10][C@H:9]([C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[C@@H:8]([NH:7][CH2:6][CH2:5][O:4][C:3]1[C:19]([CH3:32])=[CH:20][C:21]([C:34]2[CH:42]=[CH:41][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=2[CH3:43])=[CH:22][C:2]=1[CH3:1])[CH3:18]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 821314-Bromo-3-methylbenzoic acidHCID 685445484-((1R,2S)-2-{2-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethylamino}-1-hydroxypropyl)phenol

Product 1

HCID 103890224'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-2,3',5'-trimethylbiphenyl-4-carboxylic acidYield 22.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-((1R,2S)-2-{2-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethylamino}-1-hydroxypropyl)phenol (0.02 g), 4-bromo-3-methylbenzoic acid (0.020 g), tetrakis(triphenylphosphine)palladium (0.0027 g), cesium fluoride (0.041 g), 1,4-dioxane (0.75 mL), ethanol (0.25 mL) and water (0.15 mL) was stirred at 100° C. over night. After being cooled to room temperature, the reaction mixture was diluted with tetra hydrofuran (2.5 mL). The crude product was purified by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetra hydrofuran, washing solvent: tetra hydrofuran, eluent: 2 mol/L ammonia in methanol), followed by reverse phase column chromatography (Shiseido Capcell Pak C18 ODS, 5 μm, 120 Å, 20×50 mm, linear gradient 0.1% aqueous formic acid/acetonitrile=90/10-60/40) to afford the title compound (0.0046 g) as a white amorphous. The structure and physical data were shown in table 1.

Workup

  1. temperatureAfter being cooled to room temperature
  2. customThe crude product was purified by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetra hydrofuran, washing solvent: tetra hydrofuran, eluent: 2 mol/L ammonia in methanol)

Sources & evidence

ORD record
ord-9d2c1c3fe808442388a09c62c65dd30e
Source dataset
uspto-grants-2010_03
Patent number
US07674938B2

Reaction notes

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