Diisopropylamine → 4-(4-But-2-ynyloxybenzenesulfonyl)-piperidine-1,4-dicarboxylic Acid tert-butyl Ester Methyl Ester

HRID 278345Notes

Reaction equation

HRID 278345 reaction equation
C(NC(C)C)(C)C.[Li]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])C.[CH2:31]([O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42](F)(=[O:44])=[O:43])=[CH:38][CH:37]=1)[C:32]#[C:33][CH3:34]>C1COCC1>[CH3:13][O:15][C:16]([C:18]1([S:42]([C:39]2[CH:38]=[CH:37][C:36]([O:35][CH2:31][C:32]#[C:33][CH3:34])=[CH:41][CH:40]=2)(=[O:44])=[O:43])[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]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 111955204-But-2-ynyloxybenzenesulfonyl fluorideHCID 178418339Butyllithium

Product 1

HCID 117513334-(4-But-2-ynyloxybenzenesulfonyl)-piperidine-1,4-dicarboxylic Acid tert-butyl Ester Methyl EsterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of diisopropylamine (1.58 mL, 11.3 mmol) in THF (25 mL) at 0° C. was added 2.5M n-BuLi(4.68 mL, 11.7 mmol) and the resulting mixture was stirred for 15 min at that temperature. The reaction mixture was cooled to −78° C. and a solution of 1-(tert-butyl)-4-methyl 1,4-piperidinecarboxylate (prepared from example 30, step 1) (2.67 g, 11.0 mmol) in THF (40 mL) was added. The resulting mixture was stirred for 1 h and a solution of 4-but-2-ynyloxy benzenesulfonyl fluoride (2.5 g, 11.0 mmol) in THF (25 mL) was added into it. After stirring for 4 h at rt, the reaction was quenched with satd. aqueous NH4Cl solution and extracted with EtOAc, dried over anhydrous Na2SO4. The crude product was purified by silica gel chromatography to obtain 2.6 g(53%) of the product as a solid; 1H NMR(300 MHz, CDCl3) δ1.44(s, 9H), 1.87(m, 3H), 1.98(m, 2H), 2.32(m, 2H), 2.62(m, 2H), 3.74(s, 3H), 4.17(m, 2H), 4.74(m, 2H), 7.09(d, 2H, J=7.2 Hz), 7.71(d, 2H, J=7.2 Hz).

Workup

  1. stirringThe resulting mixture was stirred for 1 h
  2. stirringAfter stirring for 4 h at rt
  3. customthe reaction was quenched with satd
  4. extractionaqueous NH4Cl solution and extracted with EtOAc
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-76fdcec4bcd34f0da3c3c05fb56e81c4
Source dataset
uspto-grants-2002_03
Patent number
US06358980B1

Reaction notes

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