Ethanol → (S)-1,3,4,5-tetrahydro-4-[[(phenylmethoxy)carbonyl]amino]-3-oxo-2H-2-benzazepine-2-acetic acid, ethyl ester

HRID 1318

Reaction equation

HRID 1318 reaction equation
[C:1]1(=[O:29])[N:5]([C@H:6]2[CH2:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[CH2:9][N:8]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:7]2=[O:23])C(=O)C2=CC=CC=C12.C(O)C.C(N(CC)CC)C.[CH2:40]([O:47]C(Cl)=O)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>O.NN.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:41]1([CH2:40][O:47][C:1]([NH:5][C@H:6]2[CH2:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[CH2:9][N:8]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:7]2=[O:23])=[O:29])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 86751053(S)-1,3,4,5-tetrahydro-4-phthalimido-3-oxo-2H-2-benzazepine-2-acetic acid, ethyl ester

Product 1

HCID 86749789(S)-1,3,4,5-tetrahydro-4-[[(phenylmethoxy)carbonyl]amino]-3-oxo-2H-2-benzazepine-2-acetic acid, ethyl ester

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×HCID 24654Hydrazine hydrate (1:1)Solvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-1,3,4,5-tetrahydro-4-phthalimido-3-oxo-2H-2-benzazepine-2-acetic acid, ethyl ester (1.67 g., 4.26 mmol.) in 1.0M hydrazine hydrate in ethanol (9.0 ml., 9.0 mmol.) was stirred at room temperature under argon for 36 hours. The mixture was diluted with an equal volume of ethyl acetate, filtered and filtrate evaporated to dryness. The residue was taken up in toluene and again evaporated to dryness. The colorless, semi-solid residue (1.81 g.) was taken up in dry methylene chloride (20 ml.), placed in an ice bath and treated successively with triethylamine (0.80 ml., 5.8 mmol.) and benzylchloroformate (0.77 ml., 5.4 mmol.). After stirring at 0° C. for 2 hours, the mixture was partitioned between ethyl acetate-5% potassium bisulfate. The organic phase was washed successively with 5% potassium bisulfate, saturated sodium bicarbonate and saturated sodium chloride solutions, dried (sodium sulfate), and evaporated to dryness. Purification of the crude product by flash chromatography on silica gel (Whatmann LPS-1) eluting with ethyl acetate:hexane (1:2) gave 1.0747 g. of product as a colorless foam; Rf =0.52 (ethyl acetate:toluene, 3:7). A sample crystallized from hexane had m.p. 80°-82° C.; [α]D =+87.2° (c=0.53, chloroform).

Workup

  1. filtrationfiltered
  2. customfiltrate evaporated to dryness
  3. customagain evaporated to dryness
  4. customplaced in an ice bath
  5. customthe mixture was partitioned between ethyl acetate-5% potassium bisulfate
  6. washThe organic phase was washed successively with 5% potassium bisulfate, saturated sodium bicarbonate and saturated sodium chloride solutions
  7. dry with materialdried (sodium sulfate)
  8. customevaporated to dryness
  9. customPurification of the crude product by flash chromatography on silica gel (Whatmann LPS-1)
  10. washeluting with ethyl acetate:hexane (1:2)
  11. customgave 1.0747 g
  12. customA sample crystallized from hexane
  13. custom[α]D =+87.2° (c=0.53, chloroform)

Sources & evidence

ORD record
ord-32bc0b3ba19f4eee8fecd0b31789e6b2
Source dataset
uspto-grants-1998_03
Patent number
US05723602

Linked notes

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