Triethylamine → HCID 131710216, compound

HRID 1076422Notes

Reaction equation

HRID 1076422 reaction equation
[NH:1]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][CH2:17][C:18](O)=[O:19])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].C(N(CC)CC)C.C(Cl)(=O)OCC(C)C.[NH:46]1[CH2:57][CH2:56][CH2:55][C@H:47]1[C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49]>O1CCCC1.CN(C)C=O>[NH:1]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][CH2:17][C:18]([N:46]1[CH2:57][CH2:56][CH2:55][C@H:47]1[C:48]([O:50][C:51]([CH3:53])([CH3:54])[CH3:52])=[O:49])=[O:19])=[O:15])[CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 6453108L-Proline 1,1-dimethylethyl esterHCID 53869276HCID 53869276, compound

Product 1

HCID 131710216HCID 131710216, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

15.5 g of Z-Gly-Phe-Gly-OH [manufactured according to J. R. Vaughan & J. A. Eichler, J.Am.Chem.Soc. 75, 5556 (1953)] are dissolved in 100 ml of absolute tetrahydrofurane and 5.3 ml of absolute triethylamine and 4.64 ml of isobutyl chlorocarbonate are added dropwise to the solution cooled to -20°C, whilst stirring, in such a way that the internal temperature does a way that the internal temperature does not exceed -15°C. Thereafter the mixture is allowed to react for 10 minutes at -10°C, is then again cooled to -20°C, and a solution of 7.6 g of H-Pro-OtBu in 30 ml of dimethylformamide is added dropwise whilst stirring, in such a way that the internal temperature does not exceed 0°C. The mixture is allowed to stand for 18 hours at 0°C, the triethylamine hydrochloride is then filtered off and the filtrate is evaporated at 40°C bath temperature. The residue is dissolved in 200 ml of ethyl acetate and the solution is washed with sodium bicarbonate solution, water, 10 % strength tartaric acid solution and water, dried with sodium sulphate and evaporated. The residue is crystallised from ethyl acetate-petroleum ether, melting point 66°- 71°C; [α]D20 = - 45° (c = 1% in chloroform).

Workup

  1. customdoes not exceed -15°C
  2. customto react for 10 minutes at -10°C
  3. temperatureis then again cooled to -20°C
  4. stirringwhilst stirring
  5. customdoes not exceed 0°C
  6. filtrationthe triethylamine hydrochloride is then filtered off
  7. customthe filtrate is evaporated at 40°C bath temperature
  8. dissolutionThe residue is dissolved in 200 ml of ethyl acetate
  9. washthe solution is washed with sodium bicarbonate solution, water, 10 % strength tartaric acid solution and water
  10. dry with materialdried with sodium sulphate
  11. customevaporated
  12. customThe residue is crystallised from ethyl acetate-petroleum ether, melting point 66°- 71°C
  13. custom[α]D20 = - 45° (c = 1% in chloroform)

Sources & evidence

ORD record
ord-f9042ec9417f476388d39602136febc0
Source dataset
uspto-grants-1976_05
Patent number
US03956260

Reaction notes

Loading…