Ethyl Acetate → HCID 67385182, compound

HRID 2360963Notes

Reaction equation

HRID 2360963 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)=[O:4].C([N-]C(C)C)(C)C.[Li+].[CH:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][C:35]([CH2:38]Br)=[CH:34][CH:33]=2)=[CH:28][CH:27]=1.C(OCC)(=O)C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:38][C:35]2[CH:36]=[CH:37][C:32]([C:29]3[CH:28]=[CH:27][CH:26]=[CH:31][CH:30]=3)=[CH:33][CH:34]=2)[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]1)=[O:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2577161,1'-Biphenyl, 4-(bromomethyl)-HCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 67385182HCID 67385182, 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-methyl ester (13.19 mmol; 3.21 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; 15.83 mmol; 7.92 mL). The resulting solution was stirred at −78° C. for 2 hours. 4-Biphenylmethyl bromide (15.83 mmol; 3.91 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-biphenyl-4-ylmethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester. MS (ESI) m/z 432.3 [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-858c76b9d017448aaf88174bd4285c67
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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