Acetic Anhydride → 4-Acetyl-5-[(benzyloxy)methyl]-1-(4-fluorobenzyl)piperazin-2-one

HRID 2109846Notes

Reaction equation

HRID 2109846 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:12][N:11]1[CH2:13][C:14]([O:16]C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.B(F)(F)F.[CH3:31][CH2:32][O:33]CC.C(N(CC)CC)C.C(OC(=O)C)(=O)C>ClCCl.CN(C1C=CN=CC=1)C>[C:32]([N:11]1[CH:10]([CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][N:24]([CH2:23][C:22]2[CH:25]=[CH:26][C:19]([F:18])=[CH:20][CH:21]=2)[C:14](=[O:16])[CH2:13]1)(=[O:33])[CH3:31]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8000Boron trifluoride etherateHCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 57634653Methyl {2-[(benzyloxy)methyl]aziridin-1-yl}acetate

Product 1

HCID 576346344-Acetyl-5-[(benzyloxy)methyl]-1-(4-fluorobenzyl)piperazin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of methyl {2-[(benzyloxy)methyl]aziridin-1-yl}acetate (0.4 g, 1.7 mmol), 4-fluorobenzylamine (0.38 g, 3.3 mmol), and boron trifluoride etherate (50 μL) was heated in a sealed glass tube at 95° C. for 68 h (Bull. Chem. Soc. Jpn., 1986, 59, 321). The resulting mixture was dissolved in dichloromethane (50 mL), cooled to 0° C., and treated with a mixture of triethylamine (0.95 mL, 6.8 mmol), DMAP (21 mg, 0.17 mmol), and acetic anhydride (0.48 mL, 5.1 mmol). The mixture was stirred at room temperature overnight, and extracted successively with saturated aqueous solution of sodium bicarbonate, dilute aqueous HCl, and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a mixture of 2% methanol in ethyl acetate. Collection and concentration of appropriate fractions provided the title piperazinone.

Workup

  1. temperaturecooled to 0° C.
  2. extractionextracted successively with saturated aqueous solution of sodium bicarbonate, dilute aqueous HCl, and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. additionThe residue was subjected to column chromatography on silica gel eluting with a mixture of 2% methanol in ethyl acetate
  8. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-1c03894fc7fa49e5998dcee1d55d2404
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

Loading…