Ethyl Acetate → N~2~-[(2S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl]-N~6~-(trifluoroacetyl)-L-lysine

HRID 1430729Notes

Reaction equation

HRID 1430729 reaction equation
[CH2:1]([O:3][C:4]([CH:6]([NH:15][C@H:16]([C:28]([OH:30])=[O:29])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].C(OCC)(=O)C.O.C(O)(=O)C(O)=O>CCCCCC>[CH2:1]([O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:28]([OH:30])=[O:29])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:27])[C:23]([F:24])([F:25])[F:26])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 122529616153-56-6HCID 86593773N2-(1-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine

Product 1

HCID 10296454N~2~-[(2S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl]-N~6~-(trifluoroacetyl)-L-lysineYield 58%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

10 g of crude N2-[1-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine rich in 1S-isomer (the molar ratio of the 1S- to the 1R-isomer was 80:20) was suspended in 10-fold volume mixed solutions of 80 ml of ethyl acetate and 20 ml of n-hexane. 1.46 g (0.5 eq.) of oxalic acid monohydrate was added, and the reaction mixture was stirred at room temperature for 24 hrs. The reaction mixture was filtered, and the filtrate was concentrated to dryness under reduced pressure at a temperature lower than 40° C. The filtered cake was dissolved in 80 ml water, and 1N sodium hydroxide solution was added to adjust the pH value to 4.0 to 6.0. The solution was cooled to 0 to 5° C., and stirred for 3 hrs. After filteration, and the solid was dried in vacuum at a temperature lower than 40° C. to give 5.8 g of pure N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine. The yield is 58%, and the molar ratio of the 1S- to the 1R-isomer is 99.0:1.0.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated to dryness under reduced pressure at a temperature lower than 40° C
  3. dissolutionThe filtered cake was dissolved in 80 ml water
  4. addition1N sodium hydroxide solution was added
  5. temperatureThe solution was cooled to 0 to 5° C.
  6. stirringstirred for 3 hrs
  7. customAfter filteration, and the solid was dried in vacuum at a temperature lower than 40° C.

Sources & evidence

ORD record
ord-55d8b05e6de3402186bfd5dd2c148b8c
Source dataset
uspto-grants-2015_01
Patent number
US08940929B2

Reaction notes

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