Ethylbenzene → HCID 67037408, compound

HRID 2381173Notes

Reaction equation

HRID 2381173 reaction equation
[Li+].CC([N-]C(C)C)C.C(C1C=CC=CC=1)C.[CH2:17]([O:19][C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21])[CH3:18].Cl[CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1>[CH2:17]([O:19][C:20]([C:22]1([CH2:36][O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:24][CH2:23]1)=[O:21])[CH3:18]

Participants

6

Reactant 4

HCID 7500EthylbenzeneHCID 137983Benzyl chloromethyl etherHCID 2724682Lithium diisopropylamideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 67037408HCID 67037408, compoundYield 78.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a pre-cooled THF solution under an argon atmosphere was added at −5° C. LDA (2 M, in THF/hepatane/ethylbenzene, 17.5 ml) and then dropwise a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (5 g) in THF, keeping the temperature at about −7° C. The mixture was stirred 2 hours between −10 and −5° C. then treated slowly and dropwise with benzyl chlormethyl ether (5.47 g) at −5° C. The mixture was stirred 1 hour at 0° C. and 48 h at RT. The solvent was evaporated off, the residue partitioned between AcOEt and water. The layers were separated, the organic layer washed with brine, dried over sodium sulphate and concentrated in vacuo. The residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 5%) to give the desired 4-Benzyloxymethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (5.79 g) as a light brown oil. MS (ESI): 378.4 (MH+).

Workup

  1. customat about −7° C
  2. stirringThe mixture was stirred 1 hour at 0° C. and 48 h at RT
  3. customThe solvent was evaporated off
  4. customthe residue partitioned between AcOEt and water
  5. customThe layers were separated
  6. washthe organic layer washed with brine
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 5%)

Sources & evidence

ORD record
ord-75f3378550d74f67b8f27f2b4f64df36
Source dataset
uspto-grants-2012_09
Patent number
US08258158B2

Reaction notes

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