Triethylamine → N,N'-Dicyclohexylurea

HRID 1583281Notes

Reaction equation

HRID 1583281 reaction equation
C1(C)C=CC(S(N[C@H](C(O)=O)C)(=O)=[O:8])=CC=1.ON1C2C=CC=CC=2N=N1.[CH:27]1([N:33]=[C:34]=[N:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.COC1C=C(O)C=C(OC)C=1.C(N(CC)CC)C>C(OCC)(=O)C>[CH:36]1([NH:35][C:34]([NH:33][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)=[O:8])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 103833,5-DimethoxyphenolHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 737622N-Tosyl-L-alanine

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

For reaction by the active ester process, 14.6 g. (0.06 mol) N-(toluene-4-sulphonyl)-L-alanine and 12.2 g. (0.09 mol) N-hydroxybenzotriazole are dissolved in 300 ml. anhydrous ethyl acetate, cooled to 0° C. and mixed with 12.4 g. (0.06 mol) dicyclohexylcarbodiimide. For the formation of the active ester, the reaction mixture is stirred for 2 hours at 0° C. and then for a further 2 hours at ambient temperature. After the addition of 6.2 g. (0.04 mol) 3,5-dimethoxyphenol and 5.5 ml. (0.04 mol) triethylamine, the reaction mixture is stirred for 15 hours at ambient temperature. The N,N'-dicyclohexylurea formed is filtered off with suction and the filtrate is evaporated in a vacuum at a maximum bath temperature of 50° C. The residue is taken up in 200 ml. ethyl acetate and successively washed, in each case three times, with 100 ml. amounts of 5% citric acid and then with 100 ml. amounts of 5% sodium bicarbonate solution. After drying with anhydrous sodium sulphate, the organic phase is evaporated in a vacuum. The oily crude product obtained is purified column chromatographically with a silica gel column, using toluene-ethyl acetate (4:1 v/v) as elution agent. After evaporating the appropriately collected fractions, the residue is dissolved in a little methylene chloride and the product precipitated out by the addition of diethyl ether, there being obtained 5.8 g. (38% of theory) 1-[N-(toluene-4'-sulphonyl)-L-alanyloxy]-3,5-dimethoxybenzene in the form of colorless crystals; m.p. 110° C.; αD20 : -52.5° (c=1% in acetone).

Workup

  1. additionmixed with 12.4 g
  2. additionAfter the addition of 6.2 g

Sources & evidence

ORD record
ord-6deae88a99cc4711af69a4bff74241a0
Source dataset
uspto-grants-1985_11
Patent number
US04551428

Reaction notes

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