HCID 66732449, compound → HCID 131730477, compound

HRID 1963584Notes

Reaction equation

HRID 1963584 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][CH:7]2[CH2:12][CH:11]([C:13](=[C:15]3C(=O)O[C:18](C)([CH3:22])[O:17][C:16]3=[O:24])[OH:14])[CH2:10][CH2:9][N:8]2[C:25]([O:27][CH3:28])=[O:26])=[CH:4][CH:3]=1>CCO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@H:7]2[CH2:12][C@H:11]([C:13](=[O:14])[CH2:15][C:16]([O:17][CH2:18][CH3:22])=[O:24])[CH2:10][CH2:9][N:8]2[C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@H:7]2[CH2:12][C@@H:11]([C:13](=[O:14])[CH2:15][C:16]([O:17][CH2:18][CH3:22])=[O:24])[CH2:10][CH2:9][N:8]2[C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=1

Participants

4

Reactant 1

HCID 66732449HCID 66732449, compound

Product 2

HCID 131730476HCID 131730476, compoundYield 13%HCID 131730477HCID 131730477, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 2-(4-chlorobenzyl)-4-((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(hydroxy)-methyl)piperidine-1-carboxylate (7.00 g, 16 mmol) was dissolved in EtOH (100 mL) to give a yellow solution. The mixture was warmed up to almost reflux and stirred for 90 min. The solvent was evaporated and the residue was purified via Biotage (heptane:ethyl acetate, gradient 20%->70% ethyl acetate, 7 CV, 340 g column, two runs) to yield trans-methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (780 mg, 13%) and cis-methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.45 g, 24%) Cis-isomer: 1H NMR (400 MHz, cdcl3) δ 1.14-1.31 (m, 3H), 1.56-1.95 (m, 4H), 2.59-3.08 (m, 4H), 3.43 (d, 2H), 3.59 (d, 3H), 3.80-3.95 (m, 1H), 4.00-4.22 (m, 3H), 7.05-7.11 (m, 2H), 7.18-7.24 (m, 2H). MS m/z 382, 384 (M+H)+. Trans-isomer: 1H NMR (400 MHz, cdcl3) δ 1.26 (t, 3H), 1.39-1.99 (m, 4H), 2.46-3.06 (m, 4H), 3.35-3.72 (m, 5H), 3.95-4.32 (m, 3H), 4.40-4.72 (m, 1H), 6.99-7.37 (m, 4H). MS m/z 382, 384 (M+H)+

Workup

  1. customto give a yellow solution
  2. temperatureThe mixture was warmed up
  3. temperatureto almost reflux
  4. customThe solvent was evaporated
  5. customthe residue was purified via Biotage (heptane:ethyl acetate, gradient 20%->70% ethyl acetate, 7 CV, 340 g column, two runs)

Sources & evidence

ORD record
ord-15939347adb6492d914ec4d22a3fb203
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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