Trifluoroacetic acid → benzyl 2-(methylamino)ethylcarbamate

HRID 1179308Notes

Reaction equation

HRID 1179308 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][NH2:5].C(O)(C(F)(F)F)=O.[CH2:13]([O:20][C:21](ON1C(=O)CCC1=O)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1OCCOCCOCCOCCOCCOC1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>>[CH3:1][NH:2][CH2:3][CH2:4][NH:5][C:21](=[O:22])[O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8014N-MethylethylenediamineHCID 10236NinhydrinHCID 2855718-Crown-6HCID 83172Benzyl succinimido carbonate

Product 1

HCID 10822258benzyl 2-(methylamino)ethylcarbamateYield 355.7%

Procedure

To a solution of N-methyl ethylene diamine (10 g, 135 mmol) in CHCL3 (100 mL) was added TFA (11.43 mL, 148.4 mmol) and the solution was stirred for several minutes. The reaction was then treated successively with 1-{[(benzyloxy)carbonyl]oxy}pyrrolidine-2,5-dione (Aldrich, 43.7 g, 175.3 mmol) and 18-crown-6 (71.3 g, 269.8 mmol). The reaction became slightly green. After stirring for 1 hour at room temperature, TLC (ninhydrin stain) showed no remaining starting amine. The reaction was transferred to a separatory funnel and washed with KOH solution. The aqueous layer was back-extracted several times. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give 100 g of a yellow oil. The oil was dissolved in 300 ml CHCl3 and half of this volume was chromatographed on silica (150 mm×7 inches, 1 Kg silica gel, packed in CHCl3) eluting with CHCl3 saturated NH3. The pure fractions were collected and the remaining half of the crude chromatographed in the same way. Product fractions contaminated with some bis-CBZ protected material were dissolved in CHCl3 and washed with acid water. The aqueous was then basified and extracted with CHCl3. The organic layer was dried over Na2SO4, filtered and concentrated with the other pure fractions to give the product as a clear, colorless oil.

Workup

  1. stirringAfter stirring for 1 hour at room temperature
  2. customThe reaction was transferred to a separatory funnel
  3. washwashed with KOH solution
  4. extractionThe aqueous layer was back-extracted several times
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f309dc1fdab648eb92276d0bd2a84a99
Source dataset
uspto-grants-2007_10
Patent number
US07279487B2

Reaction notes

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