Triethylamine → Boc-Gly-Gly-Phe-Met-OMe

HRID 127605Notes

Reaction equation

HRID 127605 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:2][C:3]([NH:5][CH2:6][C:7]([OH:9])=O)=[O:4].C(N(CC)CC)C.ClC(OCC)=O.[NH2:30][C@H:31]([C:39]([NH:41][C@H:42]([C:47]([O:49][CH3:50])=[O:48])[CH2:43][CH2:44][S:45][CH3:46])=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.Cl>CN(C=O)C>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:30][C@H:31]([C:39]([NH:41][C@H:42]([C:47]([O:49][CH3:50])=[O:48])[CH2:43][CH2:44][S:45][CH3:46])=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:9])=[O:4]

Participants

6

Reactant 4

HCID 8471Triethylamine3×HCID 10928Ethyl chloroformateHCID 3334662-(2-{[(Tert-butoxy)carbonyl]amino}acetamido)acetic acid2×HCID 67685067H-Phe-Met-OMe.HCl

Product 1

HCID 10907488Boc-Gly-Gly-Phe-Met-OMe

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

4.43 g of Boc-Gly-Gly-OH, A (2) is dissolved in 30 ml DMF and cooled to 0° C., after which 1 equivalent TEA (triethylamine) is added. The mixture is cooled further to about -10° C., after which 1 equivalent (eq) ethyl chloroformate is added and the whole is stirred for about 10 minutes. 6.6 g H-Phe-Met-OMe.HCl (A.1) in 30 ml DMF and 1.1 eq TEA is then added to the mixture, which is stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature. After cooling to about -10° C., TEA.HCl is separated by filtration and the filtrate is evaporated to dryness. The residue is dissolved in 235 ml EtOAc and 55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution. The solution is then dried over Na2SO4 filtered and evaporated to dryness. Melting point 100°-101° C.; Rf in CHCl3 :CH3OH:Wa (70:30:5)=0.94 on SiO2.

Workup

  1. temperatureThe mixture is cooled further to about -10° C.
  2. stirringis stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature
  3. temperatureAfter cooling to about -10° C.
  4. customHCl is separated by filtration
  5. customthe filtrate is evaporated to dryness
  6. dissolutionThe residue is dissolved in 235 ml EtOAc
  7. wash55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution
  8. dry with materialThe solution is then dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-cd6dfff5a75e4db491ee5b7f079989b2
Source dataset
uspto-grants-1981_03
Patent number
US04256736

Reaction notes

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