Toluene → Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioate

HRID 1386712Notes

Reaction equation

HRID 1386712 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1CI)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]1OCCOCCOCCOCCOCCO[CH2:17]1.C(=O)([O-])[O-].[K+].[K+].C([C:42]([CH2:49]C)([C:46]([O-:48])=[O:47])[C:43]([O-:45])=[O:44])C.[C:51]1(C)C=CC=C[CH:52]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:49][CH:42]([C:46]([O:48][CH2:51][CH3:52])=[O:47])[C:43]([O:45][CH2:16][CH3:17])=[O:44])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 5

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 69515632,2-DiethylpropanedioateHCID 21180810tert-Butyl 2-(iodomethyl)piperidine-1-carboxylate

Product 1

HCID 21180611Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioateYield 89%

Conditions

Temperature
80 °C

Procedure

A mixture of 645 mg (2.0 mmol) of 1-(t-butoxycarbonyl)-4-(iodomethyl)piperidine (from EXAMPLE 32, Step A), 660 mg (2.5 mmol) of 18-crown-6, 550 mg (4.0 mmol) of potassium carbonate and 0.60 mL of diethylmalonate in 12 mL of toluene was heated at 80° C. for 20h. The mixture was cooled, partitioned between 75 mL of ether and 50 mL of H2O and the layers were separated. The organic layer was washed with 50 mL of 5% Na2S2O3, 50 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 30 g of silica gel using 4:1 v/v hexanes/EtOAc, then 2:1 v/v hexanes/EtOAc as the eluant afforded 630 mg (89%) of the title compound: 1H NMR (500 MHz) δ 1.07-1.14 (m, 21), 1.24-1.28 (m, 6H), 1.38-1.45 (m, 1H), 1.45 (s, 9H), 1.66 (d, J=13.0, 2H), 1.83-1.87 (m, 2H), 2.65 (t, J=7.5,22H), 3.41-3.45 (m, 1H), 4.07 (app d, J=12.5,22H), 4.194.22 (m, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between 75 mL of ether and 50 mL of H2O
  3. customthe layers were separated
  4. washThe organic layer was washed with 50 mL of 5% Na2S2O3, 50 mL of sat'd NaCl
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-24bff58b7f434bc1b488c3377fd54396
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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