Phenethylamine → Tert.-butyl 4'-[(2-n-butyl-6-(2phenylethylamino-carbonyl)-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate

HRID 344221Notes

Reaction equation

HRID 344221 reaction equation
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:30]=[C:31]([C:34]([OH:36])=O)[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].C(=O)=O.C(O)(C)C.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[C:59]1([CH2:65][CH2:66][NH2:67])[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>O1CCCC1>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:30]=[C:31]([C:34]([NH:67][CH2:66][CH2:65][C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)=[O:36])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 1001PhenethylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 15069195Tert.-butyl 4'-[(2-n-butyl-6-carboxy-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylateHCID 86586944Isopropanol carbon dioxide

Product 1

HCID 67572612Tert.-butyl 4'-[(2-n-butyl-6-(2phenylethylamino-carbonyl)-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

484 mg (1 mmol) of tert.-butyl 4'-[(2-n-butyl-6-carboxy-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate are dissolved in 10 ml of absolute tetrahydrofuran and cooled to -20° C. with stirring and cooling with dry ice/isopropanol. At this temperature 101 mg (1 mmol) of N-methylmorpholine are added. The resulting mixture is then cooled to -30° C. and a solution of 136 mg (1 mmol) of isobutylchloroformate dissolved in 5 ml of absolute tetrahydrofuran is slowly added dropwise. To complete the formation of the mixed anhydride the mixture is stirred for a further hour at -40° C. At -40° C. 134 mg (1.1 mmol) of 2-phenylethylamine dissolved in 2 ml of absolute tetrahydrofuran are slowly added dropwise. Then the mixture is allowed to rise slowly to ambient temperature and stirred for 16 hours at ambient temperature. The solvent is distilled off, the remaining viscous oil is taken up in saturated common salt solution/ethyl acetate and extracted 3 times in all with ethyl acetate. The ethyl acetate phases are dried over sodium sulphate and evaporated down. The viscous oil is dissolved in methylene chloride and purified over a silicon gel column (eluant: methylene chloride/ethanol 50:1 and 25:1).

Workup

  1. temperatureThe resulting mixture is then cooled to -30° C.
  2. additionis slowly added dropwise
  3. stirringis stirred for a further hour at -40° C
  4. customAt -40° C
  5. additionare slowly added dropwise
  6. customto rise slowly to ambient temperature
  7. stirringstirred for 16 hours at ambient temperature
  8. distillationThe solvent is distilled off
  9. extractionextracted 3 times in all with ethyl acetate
  10. dry with materialThe ethyl acetate phases are dried over sodium sulphate
  11. customevaporated down
  12. dissolutionThe viscous oil is dissolved in methylene chloride
  13. custompurified over a silicon gel column (eluant: methylene chloride/ethanol 50:1 and 25:1)

Sources & evidence

ORD record
ord-56bef27e55454534939772ed213ab64b
Source dataset
uspto-grants-1999_01
Patent number
US05864043

Reaction notes

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