1,2-Dichloroethane → N-Benzyloxycarbonyl-L-tert-leucine-N-2-(2-methoxy-ethoxymethoxy)ethylamide

HRID 361960Notes

Reaction equation

HRID 361960 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=O)[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC1C(O)=C(F)C(F)=C(F)C=1F.C(Cl)CCl.[CH3:36][O:37][CH2:38][CH2:39][O:40][CH2:41][O:42][CH2:43][CH2:44][NH2:45]>CN(C=O)C.C(O)C>[CH3:36][O:37][CH2:38][CH2:39][O:40][CH2:41][O:42][CH2:43][CH2:44][NH:45][C:17](=[O:19])[C@H:12]([C:13]([CH3:14])([CH3:15])[CH3:16])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 9899995(2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 19350391O-(2-methoxyethoxymethyl)ethanolamine

Product 1

HCID 22942185N-Benzyloxycarbonyl-L-tert-leucine-N-2-(2-methoxy-ethoxymethoxy)ethylamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-Benzyloxycarbonyl-L-tert-leucine (2.01 g, 7.6 mmol) was dissolved in DMF (20 ml), cooled in an ice bath and stirred during the addition of pentafluorophenol (2.83 g, 15.4 mmol) and EDC (2.95 9, 15.4 mmol). The mixture was stirred at 0° C. for for 1 hour then at room temperature for a further 2 hours. The solution was cooled back to 0° C., a solution of O-(2-methoxyethoxymethyl) ethanolamine in ethanol, prepared in StepG, was added and the reaction was allowed to stirovernight at room temperature. The solvent was removed under reduced pressure, the residue was dissolved in diethyl ether (50 ml), and the solution was washed successively with 1M sodium carbonate (2×30 ml),1M hydrochloric acid (2×30 ml) and brine (30 ml). The organic phase was dried over magnesium sulphate, filtered and evaporated to an oil whichwas purified by column chromatography (silica gel, gradient elution with 50-75% ethyl acetate in hexane). Yield: 1.79 g (67%). 1H--NMR; δ(CDCI3), 7.34 (5H, m), 6.54 (1H, m), 5.60 (1H, m), 5.11 (2H, m), 4.62 (2H, s), 3.93 (1H, d, J=9.3 Hz), 3.70 (4H, m), 3.57 (3H, m), 3.44(3H, s), 3.41 (1H, m) and 1.00 (9H, s).

Workup

  1. temperaturecooled in an ice bath
  2. waitat room temperature for a further 2 hours
  3. temperatureThe solution was cooled back to 0° C.
  4. additionwas added
  5. customto stirovernight at room temperature
  6. customThe solvent was removed under reduced pressure
  7. dissolutionthe residue was dissolved in diethyl ether (50 ml)
  8. washthe solution was washed successively with 1M sodium carbonate (2×30 ml),1M hydrochloric acid (2×30 ml) and brine (30 ml)
  9. dry with materialThe organic phase was dried over magnesium sulphate
  10. filtrationfiltered
  11. customevaporated to an oil
  12. customwhichwas purified by column chromatography (silica gel, gradient elution with 50-75% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0219a68e095842a1af5e76453780d397
Source dataset
uspto-grants-1999_02
Patent number
US05866717

Reaction notes

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