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

HRID 454003

Reaction equation

HRID 454003 reaction equation
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

Participants

5

Reactant 2

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

Product 2

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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%).

Sources & evidence

ORD record
ord-927b0147c84e4c43900680fe5de1c052
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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