Trifluoroacetic acid → Benzyl-2-[2-(tert-butoxycarbonyl)-acetamido]acetate

HRID 1616998Notes

Reaction equation

HRID 1616998 reaction equation
[CH2:1]([O:8][C:9](=[O:12])[CH2:10][NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:13](O)([C:15](F)(F)F)=[O:14].[C:20]([O:24][C:25](=[O:31])NCC(=O)N)([CH3:23])([CH3:22])[CH3:21].CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][C:9](=[O:12])[CH2:10][NH:11][C:13](=[O:14])[CH2:15][C:25]([O:24][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 409140Benzyl glycinateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 109100641,1-Dimethylethyl N-(2-amino-2-oxoethyl)carbamate

Product 1

HCID 68088972Benzyl-2-[2-(tert-butoxycarbonyl)-acetamido]acetateYield 72.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Benzyl-2-aminoacetate, TFA salt (13; 1.72 g, 5.12 mmol) and carbamoylmethyl-carbamic acid tert-butyl ester (8a; 1.13 g, 6.19 mmol) were dissolved in 40 mL dichloromethane with stirring at 0° C., followed by addition of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC; 1.33 g, 7.0 mmol) and triethylamine (1.0 mL, 7.2 mmol), and the reaction was replaced under room temperature with continuous stirring for 6 h. After the reaction was completed, dichloromethane was removed by concentration under reduced pressure. The obtained solid was dissolved in ethyl acetate (50 mL), and then the organic phase was washed by H2O, 5% citric acid, H2O, saturated NaHCO3 and saturated NaCl solution separately, and dried over MgSO4 and concentrated under reduced pressure to remove ethyl acetate to obtain colorless oil-like 14 (1.15 g; 72.6%). 1H-NMR (200 MHz) (CDCl3) δ: 7.28-7.33 (m, 5H, ArH), 6.89 (br, s, 1H, CONHCH2), 5.36 (br, s, 1H, NHBOC), 5.13 (s, 2H, CO2CH2Ph), 4.04 (d, 2H, CH2CO2CH2Ph), 3.81 (d, 2H, CH2NHBOC), 1.40 [s, 9H, CO2C(CH3)3].

Workup

  1. customwas replaced under room temperature
  2. stirringwith continuous stirring for 6 h
  3. customdichloromethane was removed by concentration under reduced pressure
  4. dissolutionThe obtained solid was dissolved in ethyl acetate (50 mL)
  5. washthe organic phase was washed by H2O, 5% citric acid, H2O, saturated NaHCO3 and saturated NaCl solution separately
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customto remove ethyl acetate

Sources & evidence

ORD record
ord-d8b039c8ed704d629c795cd32c898d27
Source dataset
uspto-grants-2014_07
Patent number
US08765934B2

Reaction notes

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