Cesium fluoride → (4'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy)-2,3',5'-trimethylbiphenyl-4-yloxy)acetic Acid

HRID 30771Notes

Reaction equation

HRID 30771 reaction equation
Br[C:2]1[CH:22]=[C:21]([CH3:23])[C:5]([O:6][CH2:7][CH2:8][NH:9][C@@H:10]([CH3:20])[C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[OH:12])=[C:4]([CH3:24])[CH:3]=1.[CH3:25][C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][C:36]=1B1OC(C)(C)C(C)(C)O1)[O:29][CH2:30][C:31]([OH:33])=[O:32].[F-].[Cs+].O1CCOCC1>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)C>[OH:12][C@H:11]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C@@H:10]([NH:9][CH2:8][CH2:7][O:6][C:5]1[C:21]([CH3:23])=[CH:22][C:2]([C:36]2[CH:35]=[CH:34][C:28]([O:29][CH2:30][C:31]([OH:33])=[O:32])=[CH:27][C:26]=2[CH3:25])=[CH:3][C:4]=1[CH3:24])[CH3:20]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 23090764HCID 23090764, compoundHCID 68543491HCID 68543491, compound

Product 1

HCID 11670172(4'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy)-2,3',5'-trimethylbiphenyl-4-yloxy)acetic AcidYield 23.3%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-{(1R,2S)-2-[2-(4-bromo-2,6-dimethylphenoxy)ethylamino]-1-hydroxypropyl}phenol (0.03 g), [3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy]acetic acid (0.045 g), tetrakis(triphenylphosphine)-palladium (0.0046 g), cesium fluoride (0.069 g), 1,4-dioxane (0.75 mL), ethanol (0.25 mL) and water (0.15 mL) was stirred at 100° C. overnight. After being cooled to room temperature, the reaction mixture was diluted with tetrahydrofuran (2.5 mL). The crude product was purified firstly by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetrahydrofuran, washing solvent:tetrahydrofuran, eluent:2 mol/L ammonia in methanol), and then 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 (0.0085 g) as a white amorphous. The structure and physical data were shown in table 2.

Workup

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

Sources & evidence

ORD record
ord-1b8902d15d364816b3a04fb12c21b179
Source dataset
uspto-grants-2008_09
Patent number
US07423185B2

Reaction notes

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