Ethyl Acetate → HCID 67385108, compound

HRID 2360971Notes

Reaction equation

HRID 2360971 reaction equation
[CH2:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[O:10])[CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:33][C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1.C(OCC)(=O)C>C1COCC1>[CH2:1]1[CH2:2][CH2:3][CH:4]([CH2:7][O:8][C:9]([C:11]2([CH2:33][C:34]3[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=3)[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[O:10])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 869964-(Bromomethyl)benzonitrileHCID 2724682Lithium diisopropylamideHCID 67384630HCID 67384630, compound

Product 1

HCID 67385108HCID 67385108, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-cyclohexylmethyl ester (6.61 mmol; 2.15 g) in dry THF (30 mL) under argon at −78° C. was added, dropwise, a 2M solution of lithium diisopropylamide (2M solution in heptanes/THF/ethylbenzene; 8.59 mmol; 4.29 mL). The resulting solution was stirred at −78° C. for 2 hours. 4-Bromomethyl-benzonitrile (6.61 mmol; 1.30 g) was added and the resulting solution was stirred at −78° C. for 2 hours, then 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-cyano-benzyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-cyclohexylmethyl ester. MS (ESI) m/z 436.38 [M+Na]+.

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-41714473f1494b808136ab209b6c7c19
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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