Potassium Carbonate → 4-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 2377942Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2377942
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C([Si](C)(C)[O:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[C:32]([F:37])[CH:31]=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C1COCC1.O>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:36][C:33]3[CH:34]=[CH:35][C:30]([CH2:29][CH2:28][OH:27])=[CH:31][C:32]=3[F:37])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 672032794-[2-(Tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol

Produkt 1

HCID 598567524-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl EsterAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (270 mg, 0.84 mmol) and 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol (279 mg, 0.84 mmol) in DMF (5 mL), was K2CO3 (137 mg, 0.84 mmol) added. The reaction mixture was irradiated under microwave for 1 hour at 150° C. The reaction was cooled to room temperature and treated with 1.0 M TBAF in THF (0.9 mL). After stirring for 2 hours, the reaction was poured into H2O (50 mL) and extracted with ethyl acetate (50 mL). The ethyl acetate was dried over MgSO4, and concentrated under vacuum and purified over SiO2 to afford the desired compound (321 mg, 89%) as a white solid. 1H NMR (400 Mz, DMSO-d6) δ 8.21 (s, 1H), 7.38˜7.37 (m, 1H), 7.29˜7.28 (m, 1H), 7.21˜7.17 (m, 1H), 5.30 (m, 1H), 4.75 (m, 1H), 3.67˜3.65 (m, 2H), 3.64˜3.41 (m, 2H), 3.33˜3.30 (m, 2H), 3.02 (m, 2H), 2.91 (s, 3H), 1.99˜1.93 (m, 2H), 1.66˜1.64 (m, 2H), 1.22 (d, 6H). LCMS 432.6 [MH+].

Aufarbeitung

  1. additionadded
  2. customThe reaction mixture was irradiated under microwave for 1 hour at 150° C
  3. extractionextracted with ethyl acetate (50 mL)
  4. dry with materialThe ethyl acetate was dried over MgSO4
  5. concentrationconcentrated under vacuum
  6. custompurified over SiO2

Quellen und Nachweise

ORD-Eintrag
ord-9fab3e8daec140f8b35cbdc2531fdf75
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470699B2

Notizen zur Reaktion

Wird geladen…