1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 131711081, compound

HRID 2083807Notes

Reaction equation

HRID 2083807 reaction equation
[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:2]([C:13]([OH:15])=[O:14])[C@@H:3]([CH3:12])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH:23]1[CH2:30][CH2:29][CH2:28][C@H:24]1[C:25]([NH2:27])=[O:26].Cl.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C1COCC1>[CH3:12][C@@H:3]([O:4][CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[C@H:2]([NH:1][C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[C:13]([OH:15])=[O:14].[NH:23]1[CH2:30][CH2:29][CH2:28][C@H:24]1[C:25]([NH2:27])=[O:26]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1549483L-Threonine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 12707183(S)-Pyrrolidine-2-carboxamide monohydrochloride

Product 1

HCID 131711081HCID 131711081, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

BOC-Thr(Bzl)-OH (67.7 g.), H-Pro-NH2.HCl (33.0 g.) and HOBT (29.6 g.) were added in THF (220 ml.). WSC (40.0 ml.) was added thereto under cooling at -5° C., stirred for 1 hour at -5° C. and then overnight at room temperature. The reaction mixture was concentrated in vacuo and ethyl acetate (800 ml.) was added to the residue, which is then washed twice with 1 N HCl (400 ml.) and twice with 5% sodium bicarbonate solution (300 ml.) and water. After dehydration by anhydrous magnesium sulfate, the organic layer was concentrated in vacuo. The oily material was charged for silicagel (450 g.) column chromatography. Developing by a mixture of benzene - ethyl acetate (1:1), ethyl acetate and methanol is this order and eluting fractions were checked by silica gel thin layer chromatography. Active fractions were collected and dissolved in ethyl acetate (500 ml.) then washed twice with 5% aqueous sodium bicarbonate (300 ml.) and water, and after drying with anhydrous magnesium sulfate, concentrated in vacuo. The residue was treated with n-hexane to obtain BOC-Thr-(Bzl)-Pro-NH2 as white powder (54.5 g., Yield: 61.4%). Rf1 = 0.48, [α]D28 = -14.0° (c=1, DMF).

Workup

  1. customovernight
  2. customat room temperature
  3. concentrationThe reaction mixture was concentrated in vacuo and ethyl acetate (800 ml.)
  4. additionwas added to the residue, which
  5. washis then washed twice with 1 N HCl (400 ml.) and twice with 5% sodium bicarbonate solution (300 ml.) and water
  6. concentrationAfter dehydration by anhydrous magnesium sulfate, the organic layer was concentrated in vacuo
  7. additionThe oily material was charged for silicagel (450 g.) column chromatography
  8. additionDeveloping by a mixture of benzene - ethyl acetate (1:1), ethyl acetate and methanol
  9. washeluting fractions
  10. customActive fractions were collected
  11. dissolutiondissolved in ethyl acetate (500 ml.)
  12. washthen washed twice with 5% aqueous sodium bicarbonate (300 ml.) and water
  13. dry with materialafter drying with anhydrous magnesium sulfate
  14. concentrationconcentrated in vacuo
  15. additionThe residue was treated with n-hexane

Sources & evidence

ORD record
ord-b540d07223304f2aa016e3eac104798e
Source dataset
uspto-grants-1978_04
Patent number
US04086221

Reaction notes

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