Benzyl Bromide → 1,3-Diphenylmethyl-2-piperidinone

Temperature

-78 °C

1-Phenylmethyl-2-piperidinone (See: Yamaguchi M, Hirao 1 (1985) "A direct synthesis of [(tert-butoxycarbonyl)methylidene]-azacycloalkanes from N-alkyllactams" J. Org. Chem., 50, 1975-1977) (3.40 g, 18 mmol) was reacted with benzyl bromide (4.84 g, 28.3 mmol) in the presence of lithium diisopropylamide (prepared by treating diisopropylamine (2.73 g, 27 mmol) with butyllithium in hexanes (2.5 M, 10.3 mL, 25.7 mmol)) in THF (45 mL) and HMPA (2.7 mL, 15.5 mmol) as described above in the preparation of Example 7. After the addition of benzyl bromide, the reaction mixture was stirred for 2 h at -78° C., and then quenched with saturated NH4Cl (50 mL). The reaction mixture was extracted with ether (3×40 mL) and the combined ether extract washed with brine (40 mL) and dried over MgSO4. The solvent was removed in vacuo, and the residue (8.40 g) thus obtained, was chromatographed over silica gel (hexanes-CHCl3 -EtOAC, 15:4:1 and then 7:2:1) to give the product lactam (3.14 g, 63%) as a colorless solid: mp 94-95° C. (CH2Cl2 -hexanes).

1. customas described above in the preparation of Example 7
2. customquenched with saturated NH4Cl (50 mL)
3. extractionThe reaction mixture was extracted with ether (3×40 mL)
4. extractionthe combined ether extract
5. washwashed with brine (40 mL)
6. dry with materialdried over MgSO4
7. customThe solvent was removed in vacuo

ORD record

ord-0f13a7a942b240b2b35878f5fe93c31f

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06066666