Triphenylphosphine → (1-Methyl-3-piperidyl)methanol

HRID 454003

Reaktionsgleichung

Reaktionsgleichung von HRID 454003
ClC1C=CC([O:6][C:7]2[C:16]3[C:11](=C[C:13](O)=[C:14](OC)[CH:15]=3)[N:10]=[CH:9]N=2)=C(F)C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH3:9][N:10]1[CH2:13][CH2:14][CH2:15][CH:16]([CH2:7][OH:6])[CH2:11]1.[CH3:9][N:10]1[CH2:13][CH2:14][CH2:15][C@@H:16]([CH2:7][OH:6])[CH2:11]1

Komponenten

5

Edukt 2

HCID 11776TriphenylphosphineHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

Produkt 2

HCID 97998(1-Methyl-3-piperidyl)methanolHCID 920113(R)-(1-methylpiperidin-3-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (12.1 g, 38 mmol), (prepared as described for the starting material in Example 5), was suspended in dichloromethane (375 ml) and treated with triphenylphosphine (29.6 g, 113 mmol) then stirred at ambient temperature for 30 minutes. (1-Methylpiperidin-3-yl)methanol (8.25 g, 63.8 mmol) and (R)-(1-methylpiperidin-3-yl)methanol (1.46 g, 11.3 mmol), (CAS 205194-11-2), giving R:S (57.5:42.5 by chiral HPLC) (9.7 g, 75 mmol) were dissolved in dichloromethane (75 ml) and added to the suspension. Diethyl azodicarboxylate (17.7 ml, 75 mmol) was added in portions using a syringe pump and the mixture was then allowed to warm to ambient temperature and stirred overnight. The residue was concentrated under vacuum then chromatographed on silica eluting with dichloromethane followed by dichloromethane/methanol/ammonia (93/6/1). The relevant fractions were combined and evaporated to give an oil. The residue was triturated with ether, filtered and dried to give (R,S)-4-(4-chloro-2-fluorophenoxy)-6-methoxy-74(1-methylpiperidin-3-yl)methoxy)quinazoline (8.7 g, 53%).

Quellen und Nachweise

ORD-Eintrag
ord-927b0147c84e4c43900680fe5de1c052
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492560B2

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