Triethylamine → Boc-Ala-Ala-OMe

HRID 928904Notes

Reaction equation

HRID 928904 reaction equation
[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([OH:6])=O)[CH3:3].[NH2:14][C@H:15]([C:17]([O:19][CH3:20])=[O:18])[CH3:16].C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C>ClCCl>[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([NH:14][C@H:15]([C:17]([O:19][CH3:20])=[O:18])[CH3:16])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 82335L-Alanine methyl esterHCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 10671868Boc-Ala-Ala-OMe

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Boc-(L)-Ala-(L)-Ala-OMe was prepared as follows. Boc-(L)-Ala-OH (2.06 g, 10.63 mmol) was dissolved in distilled dichloromethane (5 mL). To the resulting solution was added H2N-(L)-Ala-OMe (0.996 g, 9.67 mmol) in 5 mL of distilled dichloromethane. Dicyclohexylcarbodiimide (abbr. DCC; 2.19 g, 10.63 mmol) was dissolved in 3 mL distilled dichloromethane and added to the solution. Dicyclohexylurea (abbr. DCU) precipitation was noted immediately after DCC addition. Triethylamine (3 mL, 21.52 mmol) and additional distilled dichloromethane (4 mL) were added to the reaction mixture. The reaction proceeded for a total of three hours, when TLC analysis indicated consumption of H2N-(L)-Ala-OMe starting material and formation of a new component. DCU precipitation was promoted by storing the reaction at −20° C. The precipitate was filtered through a Buchner funnel and rinsed with cold dichloromethane. The combined filtrate and rinses were dried under vacuum and purified by Silica chromatography to yield dipeptide Boc-(L)-Ala-(L)-Ala-OMe (2.03 g, 7.14 mmol, 74%). 1H-NMR (chloroform-d) δ (ppm): 1.34 (d, J=14.1 Hz, 3H); 1.38 (d, J=14.3 Hz, 3H); 1.40 (s, 9H); 3.73 (s, 3H); 4.14 (s-broad, 1H); 4.55 (quintet, J=14.5 Hz, 1H); 4.97 (s-broad, 1H); 6.59 (s-broad, 1H).

Workup

  1. distillationdistilled dichloromethane
  2. additionadded to the solution
  3. customDicyclohexylurea (abbr. DCU) precipitation
  4. additionafter DCC addition
  5. additionwere added to the reaction mixture
  6. customproceeded for a total of three hours, when TLC analysis
  7. customconsumption of H2N-(L)-Ala-OMe starting material and formation of a new component
  8. customDCU precipitation
  9. customthe reaction at −20° C
  10. filtrationThe precipitate was filtered through a Buchner funnel
  11. washrinsed with cold dichloromethane
  12. customThe combined filtrate and rinses were dried under vacuum
  13. custompurified by Silica chromatography

Sources & evidence

ORD record
ord-bcb78ec925d443f89c7c765e0a1bc742
Source dataset
uspto-grants-2016_03
Patent number
US09290791B2

Reaction notes

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