Triethylamine → Methyl 2-(2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxamido)-2-methylpropanoate

HRID 405688Notes

Reaction equation

HRID 405688 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][CH:12]=[C:13]([C:15]([OH:17])=O)[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:19][C:20]([CH3:26])([CH3:25])[C:21]([O:23][CH3:24])=[O:22].C(N(CC)CC)C.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][CH:12]=[C:13]([C:15]([NH:19][C:20]([CH3:26])([CH3:25])[C:21]([O:23][CH3:24])=[O:22])=[O:17])[N:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 101990462-(((Tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylic acidHCID 13258034Methyl 2-aminoisobutyrate hydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 67991992Methyl 2-(2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxamido)-2-methylpropanoateYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a round bottom flask with 50 mL methylene chloride was added 2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxylic acid (2.0 g, 7.74 mmole) and methyl 2-amino-2-methylpropanoate hydrochloride salt (1.25 g, 8.13 mmole). To the mixture, triethylamine (5.4 mL, 38.7 mmole) was then added, followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (2.97 g, 15.5 mmole) and hydroxybenzotriazole (2.09 g, 15.5 mmole). The resulting mixture was stirred at room temperature overnight. The mixture was then diluted with methylene chloride. The mixture was then washed with water and the aqueous layer was extracted with methylene chloride. The combined organic layer was then dried over Na2SO4 and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 1:1 EtOAc/hexane to provide the desired product (2.40 g, 87% yield).

Workup

  1. washThe mixture was then washed with water
  2. extractionthe aqueous layer was extracted with methylene chloride
  3. dry with materialThe combined organic layer was then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 1:1 EtOAc/hexane

Sources & evidence

ORD record
ord-3f960c7c1d83479e8a72bbcf461efd2b
Source dataset
uspto-grants-2014_06
Patent number
US08754050B2

Reaction notes

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