Diisopropylamine → rac-4-[1-(4-Fluoro-phenyl)-2-nitro-ethyl]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

HRID 347306Notes

Reaction equation

HRID 347306 reaction equation
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[Li:8]CCCC.[CH2:13]([O:15][C:16]([CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14].[F:31][C:32]1[CH:42]=[CH:41][C:35](/[CH:36]=[CH:37]/[N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=1>C1COCC1>[Li+:8].[CH3:2][CH:1]([N-:4][CH:5]([CH3:7])[CH3:6])[CH3:3].[CH2:13]([O:15][C:16]([C:18]1([CH:36]([C:35]2[CH:41]=[CH:42][C:32]([F:31])=[CH:33][CH:34]=2)[CH2:37][N+:38]([O-:40])=[O:39])[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 53816801-Fluoro-4-((1E)-2-nitroethenyl)benzeneHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 11711547rac-4-[1-(4-Fluoro-phenyl)-2-nitro-ethyl]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl esterYield 104.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

An LDA solution was prepared by treating diisopropylamine (6.98 g, 69 mmol) with BuLi (1.6 M, 41.3 mL, 66 mmol) at −78° C. in dry THF (45 mL) under argon and allowing to warm up to −20° C. This solution was then cooled to −60° C. added to a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (15.44 g, 60 mmol) in dry THF (45 mL) at −60° C. and allowed to warm up to −40° C. over 1 h whereupon a solution of 4-fluoro-trans-beta-nitrostyrene (10.02 g, 60 mmol) in dry THF (40 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature over 1 h and then quenched with ammonium chloride (saturated, 250 mL) and the product extracted with diethylether (3×100 mL). The combined organic extracts were then washed with brine, dried over sodium sulfate, filtered and evaporated to afford the title compound (26.7 g, 99%) as a light yellow gum. MS: m/e=442.4 (M+NH4).

Workup

  1. temperatureThis solution was then cooled to −60° C.
  2. additionwas added dropwise
  3. temperatureto warm up to room temperature over 1 h
  4. customquenched with ammonium chloride (saturated, 250 mL)
  5. extractionthe product extracted with diethylether (3×100 mL)
  6. washThe combined organic extracts were then washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-36fe99860a714c73b45c1c8d70c73167
Source dataset
uspto-grants-2007_02
Patent number
US07173133B2

Reaction notes

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