Ethyl Acetate → HCID 67384774, compound

HRID 2360976Notes

Reaction equation

HRID 2360976 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].[CH3:32][O:33][C:34](=[O:43])[C:35]1[CH:40]=[CH:39][C:38]([CH2:41]Br)=[CH:37][CH:36]=1.C(OCC)(=O)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:41][C:38]2[CH:37]=[CH:36][C:35]([C:34]([O:33][CH3:32])=[O:43])=[CH:40][CH:39]=2)([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 2724682Lithium diisopropylamideHCID 222559134-Benzyl 1-tert-butyl piperidine-1,4-dicarboxylate

Product 1

HCID 67384774HCID 67384774, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of piperidine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (30.12 mmol; 9.62 g) in dry THF (100 mL) under argon at −78° C. was added, dropwise, a 2M solution of lithium diisopropylamide (2M solution in heptanes/THF/ethylbenzene; 39.16 mmol; 19.58 mL). The resulting solution was stirred at −78° C. for 2 hours. 4-Bromomethylbenzoic acid methyl ester (30.12 mmol; 6.90 g) was added and the resulting solution was stirred at −78° C. for 2 hours and allowed to warm to room temperature overnight. Ethyl acetate (150 ml) was added. The resulting solution was washed with a 1M aqueous hydrochloric acid solution (2×50 mL) and brine (50 mL) and dried over magnesium sulfate. After filtration and evaporation, the residue was purified via flash column chromatography (eluent gradient: 0 to 50% EtOAc in heptane) to yield 4-(4-methoxycarbonyl-benzyl)-piperidine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester. MS (ESI) m/z 468.20 [M+H]+.

Workup

  1. stirringthe resulting solution was stirred at −78° C. for 2 hours
  2. temperatureto warm to room temperature overnight
  3. washThe resulting solution was washed with a 1M aqueous hydrochloric acid solution (2×50 mL) and brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationAfter filtration and evaporation
  6. customthe residue was purified via flash column chromatography (eluent gradient: 0 to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-efc6c75beba94dbbac807b126aef372d
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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