Potassium Carbonate → tert-butyl 2-(3-methyl-1H-1,2,4-triazol-1-yl)propanoate

HRID 243703Notes

Reaction equation

HRID 243703 reaction equation
[CH3:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[C:13]([O:17][C:18](=[O:22])[CH:19](Br)[CH3:20])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1[N:6]=[CH:5][N:4]([CH:19]([CH3:20])[C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:22])[N:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 545327tert-Butyl 2-bromopropanoateHCID 178433329HCID 178433329, compound

Product 1

HCID 57907521tert-butyl 2-(3-methyl-1H-1,2,4-triazol-1-yl)propanoateYield 69.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-methyl-1H-1,2,4-triazole (7.3 g, 88 mmol) in DMF (75 mL) was added K2CO3 (60.7 g, 439 mmol) and 2-bromopropionic acid tert-butyl ester (14.6 mL, 88 mmol). The reaction was stirred at room temperature overnight. The mixture was diluted with EtOAc (500 mL), washed with water (×3) then brine. Dried over MgSO4 and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane (20 to 100%) to give 13 g of crude product as a 3:1 mixture of regioisomers. The mixture was purified by Chiralcel OD with a gradient from 4% to 30% IPA/Heptane. Then the first two peaks were separated with Chiracel OD column isocratically eluting with 4% IPA/Heptane. The second peak was collected as the desired single stereoisomer (R or S) (2-(3-methyl-1H-1,2,4-triazol-1-yl)propanoic acid tert-butyl ester) (3.5 g, 19%). 1H-NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 4.90 (q, J=7 Hz, 1H), 2.35 (s, 3H), 1.72 (d, J=7 Hz, 3H), 1.40 (s, 9H). ESI-MS calculated for C10H17N3O2: Exact Mass: 211.13. Found 156.05 (−tBu).

Workup

  1. washwashed with water (×3)
  2. dry with materialDried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography on silica gel
  5. washeluting with EtOAc/isohexane (20 to 100%)

Sources & evidence

ORD record
ord-7a4edb9f194d4375a9efec00dea25f94
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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