5-Chloro-3-methyl-1,2,4-thiadiazole → 2-(5-Cyanopentyl)-2-(3-methyl[1,2,4]thiadiazol-5-yl)malonic acid di-tert-butyl ester

HRID 1639572Notes

Reaction equation

HRID 1639572 reaction equation
CC(C)([O-])C.[K+].[C:7]([O:11][C:12](=[O:28])[CH:13]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]#[N:27])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])([CH3:10])([CH3:9])[CH3:8].Cl[C:30]1[S:34][N:33]=[C:32]([CH3:35])[N:31]=1>O1CCCC1>[C:7]([O:11][C:12](=[O:28])[C:13]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]#[N:27])([C:30]1[S:34][N:33]=[C:32]([CH3:35])[N:31]=1)[C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])([CH3:9])([CH3:8])[CH3:10]

Participants

5

Reactant 3

HCID 129191595-Chloro-3-methyl-1,2,4-thiadiazoleHCID 23665647Potassium tert-butoxideHCID 593780472-(5-Cyanopentyl)malonic acid di-tert-butyl ester

Product 1

HCID 667221752-(5-Cyanopentyl)-2-(3-methyl[1,2,4]thiadiazol-5-yl)malonic acid di-tert-butyl esterYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (14.6 g, 0.13 mol) followed by 2-(5-cyanopentyl)malonic acid di-tert-butyl ester (2021050) (32.3 g, 0.1 mol) was added portionwise to stirred tetrahydrofuran (150 mL). 5-Chloro-3-methyl-1,2,4-thiadiazole (2009380) (13.5 g, 0.10 mol) was then added to the slurry and the mixture was heated at reflux overnight before being quenched with water (150 mL) and extracted with dichloromethane (3×200 mL). The combined organic fractions were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (6:1 hexane/ethyl acetate) to afford 2-(5-cyanopentyl)-2-(3-methyl[1,2,4]thiadiazol-5-yl)malonic acid di-tert-butyl ester (2021051) (17.2 g, 42%) as a yellow oil.

Workup

  1. additionwas added portionwise
  2. temperaturethe mixture was heated
  3. temperatureat reflux overnight
  4. custombefore being quenched with water (150 mL)
  5. extractionextracted with dichloromethane (3×200 mL)
  6. dry with materialThe combined organic fractions were dried (MgSO4)
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by flash chromatography (6:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-359e688bd3ac45f181f9cd752b57ff38
Source dataset
uspto-grants-2012_02
Patent number
US08110577B2

Reaction notes

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