Sodium Carbonate → 3-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl Ester

HRID 1245067Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1245067
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19](=[O:28])[C:20]1[CH:25]=[C:24](Br)[C:23](O)=[CH:22][CH:21]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[Cl:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[F:37].C([O-])([O-])=[O:42].[Na+].[Na+]>COCCOC.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>[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19]([C:20]1[CH:21]=[C:22]([C:33]2[CH:34]=[CH:35][C:36]([F:37])=[C:31]([Cl:30])[CH:32]=2)[CH:23]=[CH:24][C:25]=1[OH:42])=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 692051283-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl ester

Produkt 1

HCID 113865603-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl EsterAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To 0.05 g (0.1 mmol) of above resin-bound 3-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl ester in 2.0 mL of DME were added 52.0 mg (0.3 mmol) of 3-chloro-4-fluorophenylboronic acid, 30 mg (0.03 mmol) of Pd(PPh3)4, and 0.3 mL (0.6 mmol) of 2N Na2CO3 solution. The mixture was heated to 80° C. for 12 h. The resin was washed with H2O, DMF, MeOH, DCM three times of each and cleaved with TMSBr/TFA/DCM (1:1:5) at rt for 4 h. The residue obtained after removing the solvent was purified by chromatography (DCM) to give 35 mg (70%) of title compound LC/MS (m/z): 490 (M+1)+.

Aufarbeitung

  1. washThe resin was washed with H2O, DMF, MeOH, DCM three times of each and
  2. customThe residue obtained
  3. customafter removing the solvent
  4. customwas purified by chromatography (DCM)

Quellen und Nachweise

ORD-Eintrag
ord-618671e654984eb6aff1410076b88f1c
Quelldatensatz
uspto-grants-2006_10
Patentnummer
US07122580B2

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