Dimethylformamide → HCID 70469155, compound

HRID 1982651Notes

Reaction equation

HRID 1982651 reaction equation
Cl.C(C(NC[CH:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])CC(C)C)(O)=O.O[N:28]1[C:32]2[CH:33]=[CH:34][CH:35]=CC=2N=N1.Cl.[CH3:38][O:39][C:40](=[O:43])CN.[CH:44]1(N=C=NC2CCCCC2)CCCCC1.[CH3:59][N:60](C)[CH:61]=[O:62]>C(N(CC)CC)C>[C:21]1([CH2:20][O:19][C:17]([N:13]2[CH2:14][CH2:15][CH2:16][CH:12]2[NH:28][C@H:32]([C:61]([NH:60][CH2:59][C:40]([O:39][CH3:38])=[O:43])=[O:62])[CH2:33][CH:34]([CH3:35])[CH3:44])=[O:18])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 5

HCID 6228Dimethylformamide2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 122755Glycine methyl ester hydrochlorideHCID 131714759HCID 131714759, compound

Product 1

HCID 70469155HCID 70469155, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
-5 °C

Procedure

To a 500 flask containing 7.33 g [S-(R*,R*)]-2-[[(1-carboxy-3-methyl butyl)amino]methyl]-1-pyrrolidinecarboxylic acid, phenylmethyl ester hydrochloride add 150 ml dimethylformamide and cool to -5° C. Add 2.57 g 1-hydroxybenzotriazole, 2.39 g glycine methyl ester hydrochloride, and 5.35 ml triethylamine. Add a solution of 3.98 g dicyclohexylcarbodiimide in 50 ml dimethylformamide over five minutes. Stir and allow to warm to 25° C. overnight. Filter and strip filtrate in vacuo to a paste. Take up into 100 ml ethyl acetate and filter. Wash filtrate once with 75 ml water, twice with 50 ml saturated sodium bicarbonate solution and once with 25 ml sodium chloride solution. Dry organic phase over anhydrous magnesium sulfate, filter and strip in vacuo to an oil. Chromatograph on 200 g silica gel, eluting with 5/95 methanol/chloroform, recovering an oil, 1.41 g, 18% yield. Rf 0.52 on Merck SG60 TLC plates, eluted with 10/90 methanol/chloroform.

Workup

  1. temperatureto warm to 25° C. overnight
  2. filtrationFilter
  3. filtrationfilter
  4. filtrationDry organic phase over anhydrous magnesium sulfate, filter
  5. washChromatograph on 200 g silica gel, eluting with 5/95 methanol/chloroform
  6. customrecovering an oil, 1.41 g, 18% yield
  7. washRf 0.52 on Merck SG60 TLC plates, eluted with 10/90 methanol/chloroform

Sources & evidence

ORD record
ord-63204c3b61ee4f469f88d431fb41c4cb
Source dataset
uspto-grants-1986_06
Patent number
US04596819

Reaction notes

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