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Sodium Carbonate → (R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

HRID 70825
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 70825
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:16][C:17](=[O:27])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.[F:28][C:29]1[CH:30]=[CH:31][C:32]([O:38][CH3:39])=[C:33](B(O)O)[CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[CH2:14]([O:13][C:11](=[O:12])[CH2:10][C@H:9]([NH:16][C:17](=[O:27])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:31]2[CH:30]=[C:29]([F:28])[CH:34]=[CH:33][C:32]=2[O:38][CH3:39])=[CH:3][CH:4]=1)[CH3:15]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 59607774(R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate

Produkt 1

HCID 67208801(R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397
HCID 178418397, Verbindung
Katalysator
HCID 702EthanolLösungsmittel
HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of (R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate, intermediate 9, (100 mg, 0.23 mmol) and 5-fluoro-2-methoxyphenylboronic acid (57.6 mg, 0.34 mmol) in toluene (1 mL) and EtOH (0.1 mL) is added Pd(PPh3)4 (26.1 mg, 0.023 mmol) and Na2CO3 (47.9 mg, 0.45 mmol). After stirring at 95° C. under nitrogen for 18 hours, the solution is cooled to ambient temperature and then quenched with aqueous 1 M HCl. The crude is diluted with ethyl acetate, the organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 30:70) to give (R)-tert-butyl 4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate (65 mg). HPLC retention time=1.44 minutes (condition B); MS (m+1)=488.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (t, J=7.1 Hz, 3 H) 1.48 (s, 9 H) 2.41-2.48 (m, 2 H) 2.51-2.63 (m, 4 H) 2.90 (dd, J=13.6, 6 Hz, 1 H) 3.02 (dd, J=13.6, 6 Hz, 1 H) 3.81 (s, 3 H) 4.14-4.29 (m, 2 H) 4.49-4.63 (m, 1 H) 6.44 (d, J=8.6 Hz, 1 H) 6.89-6.97 (m, 1 H) 6.98-7.05 (m, 1 H) 7.05-7.11 (m, 1 H) 7.27 (d, J=8.1 Hz, 2 H) 7.49 (d, J=8.1 Hz, 2 H).

Aufarbeitung

  1. temperaturethe solution is cooled to ambient temperature
  2. customquenched with aqueous 1 M HCl
  3. additionThe crude is diluted with ethyl acetate
  4. washthe organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue is purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 30:70)

Quellen und Nachweise

ORD-Eintrag
ord-2a7566d6ee1f4475bfed1307cb623dce
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08822534B2

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