Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1) → methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylate

HRID 18925Notes

Reaction equation

HRID 18925 reaction equation
C[O-].[Na+].CC1C=CC(S(O[C:15]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:16][C:17]#[N:18])(=O)=O)=CC=1.Cl.[NH2:24][CH:25](C(OCC)=O)[C:26]([O:28][CH2:29]C)=[O:27]>CO>[NH2:18][C:17]1[CH:16]=[C:15]([C:19]([CH3:20])([CH3:21])[CH3:22])[NH:24][C:25]=1[C:26]([O:28][CH3:29])=[O:27]

Participants

5

Reactant 3

HCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 10942334Sodium MethoxideHCID 722603601-Cyano-3,3-dimethylbut-1-en-2-yl 4-methylbenzenesulfonate

Product 1

HCID 18322367methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred sodium methoxide solution (15% by weight, 80 mL total) was added drop-wise a solution of 1-cyano-3,3-dimethylbut-1-en-2-yl 4-methylbenzenesulfonate (10.0 g, 36 mmol) and diethyl aminomalonate hydrochloride salt (9.0 g, 43 mmol) in methanol (50 mL). After the addition was completed, the reaction was stirred at room temperature for 2 hours, the solvent was removed under vacuum and the crude product was dissolved in water and extracted with ethyl acetate. The combined organic layers was washed with brine, dried and the solvent removed under vacuum. The crude product was purified by column chromatography (silicagel, dichloromethane:methanol 95:5) to afford 2.4 g of the desired methyl 3-amino-5-tert-butyl-1H-pyrrole-2-carboxylate used as such in the next step.

Workup

  1. additionAfter the addition
  2. customthe solvent was removed under vacuum
  3. dissolutionthe crude product was dissolved in water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers was washed with brine
  6. customdried
  7. customthe solvent removed under vacuum
  8. customThe crude product was purified by column chromatography (silicagel, dichloromethane:methanol 95:5)

Sources & evidence

ORD record
ord-dbed93c467224da4b16a268bb97437de
Source dataset
uspto-grants-2010_06
Patent number
US07741479B2

Reaction notes

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