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

HRID 30770

반응식

HRID 30770 반응식
[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]

참가 물질

9

반응물 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 821314-Bromo-3-methylbenzoic acidHCID 68544548HCID 68544548, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
100 °C

실험 절차

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. overnight. After being cooled to room temperature, the reaction mixture was diluted with tetrahydrofuran (2.5 mL). The crude product was purified by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetrahydrofuran, washing solvent:tetrahydrofuran, 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.

후처리

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

출처 및 근거

ORD 기록
ord-964b0ce4b8f2449da671bdc4fee56304
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423185B2

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