1,2-Dimethoxyethane → Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 407211

Reaktionsgleichung

Reaktionsgleichung von HRID 407211
[C:1]([NH:4][C:5]1[CH:10]=[C:9](Br)[N:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=1[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:3])[CH3:2].[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[C:27]([F:34])[C:26]=1[O:35][CH3:36].[F-].[Cs+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:28]2[CH:29]=[CH:30][C:25]([Cl:24])=[C:26]([O:35][CH3:36])[C:27]=2[F:34])[N:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=1[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 441297064-Chloro-2-fluoro-3-methoxyphenylboronic acidHCID 86600141Methyl 4-acetamido-3-(benzyloxy)-6-bromopicolinate

Produkt 1

HCID 71150541Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Methyl 4-acetamido-3-(benzyloxy)-6-bromopicolinate (prepared as in Kong, L. C. C. et al. U.S. Patent Application Publication 2005/0176767; 1.5 g, 4.0 mmol), (4-chloro-2-fluoro-3-methoxyphenyl)boronic acid (1.2 g, 5.9 mmol), bis(triphenylphosphine)-palladium(II) dichloride (PdCl2(PPh3)2; 278 mg, 0.4 mmol), cesium fluoride (CsF; 1.2 g, 7.9 mmol), 1,2-dimethoxyethane (DME; 7 mL), and H2O (7 mL) were combined and heated in a Biotage microwave at 100° C. for 15 min. H2O was added to the reaction mixture, and the product was extracted with EtOAc. The combined organic extracts were washed with satd aq NaCl, dried with sodium sulfate (Na2SO4), filtered and concentrated. Flash chromatography (SiO2; 0-45% EtOAc/cyclohexane gradient) afforded methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate as a yellow solid: mp 115-120° C.; 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J=1.6 Hz, 1H), 7.66 (s, 1H), 7.59 (dd, J=8.5, 7.7 Hz, 1H), 7.45 (s, 5H), 7.24 (dd, J=8.6, 1.7 Hz, 1H), 5.13 (s, 2H), 4.03 (s, 3H), 3.99 (d, J=1.0 Hz, 3H), 1.88 (s, 3H); ESIMS m/z 459 ([M+H]+).

Aufarbeitung

  1. extractionthe product was extracted with EtOAc
  2. washThe combined organic extracts were washed with satd aq NaCl
  3. dry with materialdried with sodium sulfate (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-e25d925e87b84e21bb3210939bf99a9a
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754229B2

Verknüpfte Notizen

Wird geladen…