Triethylamine → N-[(Phenylmethoxy)carbonyl]-L-valyl-L-leucine methyl ester

HRID 1679830Notes

Reaction equation

HRID 1679830 reaction equation
[NH2:1][C@H:2]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].Cl.C(N(CC)CC)C.[NH:19]([C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])[C@H:20]([C:24](O)=[O:25])[CH:21]([CH3:23])[CH3:22].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[NH:19]([C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])[C@H:20]([C:24]([NH:1][C@H:2]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:25])[CH:21]([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 726987N-Carbobenzoxy-L-valineHCID 2723695Leucine methyl ester hydrochloride

Product 1

HCID 12814326N-[(Phenylmethoxy)carbonyl]-L-valyl-L-leucine methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 19.9 g (110 mmols) of H-Leu-OMe.HCl in 120 ml of dimethylformamide is mixed at 0° C. with 14.6 ml (105 mmols) of triethylamine. The precipitated triethylamine hydrochloride is filtered off, the filtrate added to a solution of 25.1 g (100 mmols) of Z-Val-OH in 200 ml of dimethylformamide at 0° C. and then 22.6 g (110 mmols) of dry dicyclohexylcarbodiimide are added. The batch is stirred for 1 hour at 0° C., then kept overnight in a refrigerator, filtered, and the filtrate is evaporated under a high vacuum at 40° C. The oily residue is taken up in 30 ml of ethyl acetate, the solution cooled to 0° C. and the precipitated dicyclohexylurea is filtered off. On addition of n-hexane the product crystallizes overnight out of the filtrate; it melts at 102°-105° C. Optical rotation [α]D20 =-41° (c=2.88 in methanol).

Workup

  1. filtrationThe precipitated triethylamine hydrochloride is filtered off
  2. waitkept overnight in a refrigerator
  3. filtrationfiltered
  4. customthe filtrate is evaporated under a high vacuum at 40° C
  5. temperaturethe solution cooled to 0° C.
  6. filtrationthe precipitated dicyclohexylurea is filtered off
  7. additionOn addition of n-hexane the product
  8. customcrystallizes overnight out of the filtrate
  9. customOptical rotation [α]D20 =-41° (c=2.88 in methanol)

Sources & evidence

ORD record
ord-51ddfdf400e04db79314c29bc94f8c33
Source dataset
uspto-grants-1981_06
Patent number
US04271068

Reaction notes

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