N,N'-Dicyclohexylurea → 2-Benzyloxy-5-fluoro-3-(2,2,2-trifluoroethylcarbamoyl)-benzoic acid-[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamide]

HRID 654035Notes

Reaction equation

HRID 654035 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([C:18](=[O:25])[NH:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:16][C:15]([F:26])=[CH:14][C:10]=1[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:27][CH:28]([CH:31]1[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[O:32]1)[CH2:29][NH2:30].C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O>CN(C)C=O>[OH:27][CH:28]([CH:31]1[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[O:32]1)[CH2:29][NH:30][C:11](=[O:12])[C:10]1[CH:14]=[C:15]([F:26])[CH:16]=[C:17]([C:18](=[O:25])[NH:19][CH2:20][C:21]([F:23])([F:24])[F:22])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 4277N,N'-DicyclohexylureaHCID 10868DicyclohexylcarbodiimideHCID 11971028alpha-(Aminomethyl)-2,2-dimethyl-1,3-dioxolane-4-methanolHCID 15057649HCID 15057649, compound

Product 1

HCID 150576512-Benzyloxy-5-fluoro-3-(2,2,2-trifluoroethylcarbamoyl)-benzoic acid-[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamide]

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

4.46 g (12 mmol) of 2-benzyloxy-5-fluoro-3-(2,2,2-trifluoroethylcarbamoyl)-benzoic acid is dissolved in 30 ml of dry N,N-dimethylformamide with exclusion of moisture, 1.85 g (12 mmol) of hydroxybenzotriazolel, 2.43 g (15 mmol) of 2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamine are added and the solution is cooled to -10° C. 2.68 g (13 mmol) of dicyclohexylcarbodiimide is added by portions to the cooled solution, it is stirred for 1 hour at -10° C. and 6 hours at room temperature. The precipitate of the dicyclohexylurea is then suctioned off, the filtrate is evaporated to dryness in a vacuum and the residue is dissolved in about 100 ml of ethyl acetate. The solution is shaken out with saturated bicarbonate solution and with water, dried on sodium sulfate, filtered and concentrated by evaporation and chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane. 4.22 g (8.2 mmol)=68.3% of the theoretical yield of the compound is obtained as an amorphous solid.

Workup

  1. additionare added
  2. customthe filtrate is evaporated to dryness in a vacuum
  3. dissolutionthe residue is dissolved in about 100 ml of ethyl acetate
  4. stirringThe solution is shaken out with saturated bicarbonate solution and with water
  5. customdried on sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation
  8. customchromatographed on silica gel 60 (Merck) with ethyl acetate/hexane
  9. custom4.22 g (8.2 mmol)=68.3% of the theoretical yield of the compound is obtained as an amorphous solid

Sources & evidence

ORD record
ord-66a23734b5a8444eaa8ce657ac2f4fd5
Source dataset
uspto-grants-1992_07
Patent number
US05130119

Reaction notes

Loading…