Phenyl chloroformate → (S)-2-ethoxy-3-(4-{2-[4-(phenoxycarbonylamino)phenyl]ethoxy]phenyl)propanoic acid ethyl ester

HRID 987297Notes

Reaction equation

HRID 987297 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].Cl[C:29]([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:30]>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:29]([O:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:30])=[CH:21][CH:22]=2)=[CH:10][CH:9]=1)[CH3:3]

Participants

4

Reactant 2

HCID 15891Phenyl chloroformateHCID 86595066HCID 86595066, compound

Product 1

HCID 53791640(S)-2-ethoxy-3-(4-{2-[4-(phenoxycarbonylamino)phenyl]ethoxy]phenyl)propanoic acid ethyl esterYield 96.3%

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) (0.55 g; 1.4 mmole) was dissolved in tetrahydrofuran (5 ml). Phenyl chloroformat (0.675 g; 3 mmole) was added slowly. The reaction mixture was stirred at room temperature and continuosly checked with HPLC and after 3 days was all the starting material consumed. Water was added, tetrahydrofuran evaporated and the residue extracted three times with ethyl acetate. The organic phase was dried with magnesium sulfate and evaporated. Purification of the crude product with preparative HPLC (Kromasil C8, 7 μm, 50×250 mm) using acetronitrile (70%) in ammonium acetate buffer (pH 7) as mobil phase gave 0.46 g (96.3% yield) (S)-2-ethoxy-3-(4-{2-[4-(phenoxycarbonylamino)phenyl]ethoxy]phenyl)propanoic acid ethyl ester.

Workup

  1. customconsumed
  2. additionWater was added
  3. customtetrahydrofuran evaporated
  4. extractionthe residue extracted three times with ethyl acetate
  5. dry with materialThe organic phase was dried with magnesium sulfate
  6. customevaporated
  7. customPurification of the crude product with preparative HPLC (Kromasil C8, 7 μm, 50×250 mm)

Sources & evidence

ORD record
ord-eae89079890c4c9791886c40b1c8d63d
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

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