Triethylamine → 3-[4-{2-(4-[benzyloxycarbonylamino]phenyl)ethoxy}phenyl]-(S)-2-ethoxypropanoic acid ethyl ester

HRID 987290Notes

Reaction equation

HRID 987290 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:27])[C@@H:6]([O:24][CH2:25][CH3:26])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)=[CH:10][CH:9]=1)[CH3:3].C(N(CC)CC)C.[CH2:35]([O:42][C:43](Cl)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCCC1>[CH2:2]([O:4][C:5](=[O:27])[C@@H:6]([O:24][CH2:25][CH3:26])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:43]([O:42][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:44])=[CH:21][CH:22]=2)=[CH:10][CH:9]=1)[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 86595066HCID 86595066, compound

Product 1

HCID 542299253-[4-{2-(4-[benzyloxycarbonylamino]phenyl)ethoxy}phenyl]-(S)-2-ethoxypropanoic acid ethyl esterYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-{4-[2-(4-Aminophenyl)ethoxy]phenyl}-(S)-2-ethoxypropanoic acid ethyl ester hydro chloride (described in Example 41b) (0.6 g; 1.67 mmole, triethylamine (0.17 g; 1.67 mmole) and benzylchloroformate (0.28 g; 1.67 mmole) were mixed in tetrahydrofuran. The reaction mixture was stirred at room temperature over night and then evaporated. The residue was treated with sodium hydrogencarbonate solution and diethyl ether. The organic phase was dried with magnesium sulfate and evaporated. According to NMR spectra there was starting material left. The residue was therefore dissolved in tetrahydrofuran and triethylamine and benzylchloroformate were added. The reaction mixture was stirred at room temperature then evaporated. Work-up up as described above gave a crude product which was purification with preparativ HPLC (Kromasil C8, 7 μm, 50×250 mm) using acetronitrile (70-100%) in ammonium acetate buffer (pH 7) as mobil phase gave 0.180 g (22% yield) of 3-[4-{2-(4-[Benzyloxycarbonylamino]phenyl)ethoxy}phenyl]-(S)-2-ethoxypropanoic acid ethyl ester.

Workup

  1. customevaporated
  2. additionThe residue was treated with sodium hydrogencarbonate solution and diethyl ether
  3. dry with materialThe organic phase was dried with magnesium sulfate
  4. customevaporated
  5. waitleft
  6. dissolutionThe residue was therefore dissolved in tetrahydrofuran
  7. additiontriethylamine and benzylchloroformate were added
  8. stirringThe reaction mixture was stirred at room temperature
  9. customthen evaporated
  10. customabove gave a crude product which
  11. custompurification with preparativ HPLC (Kromasil C8, 7 μm, 50×250 mm)

Sources & evidence

ORD record
ord-408282f6253b4ebfbb5669a0e0d4ade6
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

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