Ammonium Chloride → 3-Benzo[1,3]dioxol-5-ylmethyl-1-benzyl-piperidin-2-one

HRID 2354562Notes

Reaction equation

HRID 2354562 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.Br[CH2:21][C:22]1[CH:30]=[CH:29][C:25]2[O:26][CH2:27][O:28][C:24]=2[CH:23]=1.[NH4+].[Cl-]>C1CCCCC1.C1COCC1>[O:26]1[C:25]2[CH:29]=[CH:30][C:22]([CH2:21][CH:10]3[CH2:11][CH2:12][CH2:13][N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:9]3=[O:14])=[CH:23][C:24]=2[O:28][CH2:27]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 51700761-Benzyl-2-piperidoneHCID 64514231,3-Benzodioxole, 5-(bromomethyl)-HCID 178418339Butyllithium

Product 1

HCID 684532313-Benzo[1,3]dioxol-5-ylmethyl-1-benzyl-piperidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-70 °C

Procedure

1-Benzyl-piperidin-2-one (4.8 g, 25.4 mmol) in abs. THF (200 ml) is cooled to −70° C.; sec.-BuLi (23.4 ml of a 1.3 M solution in cyclohexane; 30.4 mmol) is added dropwise under an Ar atmosphere and the mixture is stirred at −70° C. for 30 min. A solution of 5-bromomethyl-benzo[1,3]dioxole (see Harrowven et al., Tetrahedron (2001), 57(29), 4447) (8.0 g, 37.2 mmol) in abs. THF (80 ml) is added dropwise, stirring is continued at −70° C. for 3 h, then at rt for 15 h. sat. aq. NH4Cl solution is added, the organic layer is separated, dried over Na2SO4 and evaporated. The oily residue is purified by MPLC (140 g silica gel, eluent cyclohexane, then cyclohexane:AcOEt 7:3) to give 3-benzo[1,3]dioxol-5-ylmethyl-1-benzyl-piperidin-2-one as a yellow oil. Preparative resolution using a Chiralpak AD 5×50 cm/20 μm column (Daicel Chiral Technologies, Inc., Exton USA; a chiral stationary phase); eluent hexane: isopropanol 90:10; flow 80 ml/min; UV detection (210 nM) gives (−)-3-benzo[1,3]dioxol-5-ylmethyl-1-benzyl-piperidin-2-one ([α]Drt=−61.1° (c=0.5, EtOH)).

Workup

  1. addition30.4 mmol) is added dropwise under an Ar atmosphere
  2. stirringstirring
  3. waitis continued at −70° C. for 3 h
  4. customthe organic layer is separated
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe oily residue is purified by MPLC (140 g silica gel, eluent cyclohexane

Sources & evidence

ORD record
ord-a3803c2d3004478c8e060faa36ce390e
Source dataset
uspto-grants-2010_07
Patent number
US07754719B2

Reaction notes

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