Oxalic Acid → HCID 20467908, compound

HRID 1903095Notes

Reaction equation

HRID 1903095 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:23])([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[CH:12]1.C([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](O)=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C(O)(=O)C(O)=O>O1CCCC1.C(OCC)(=O)C.C(OCC)C.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:23])([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:36]1[CH:35]=[CH:34][C:33]([N:30]2[CH2:29][CH2:28][NH:27][CH2:32][CH2:31]2)=[CH:38][CH:37]=1)[CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[CH:12]1

Participants

10

Reactant 5

HCID 971Oxalic AcidHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 7124411-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanoneHCID 20467910HCID 20467910, compound

Product 1

HCID 20467908HCID 20467908, compound

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution consisting of 2-(2,4-dichlorophenyl)-1-(imidazol-1-yl)octan-2,8-diol (3.5 g.), the product of Preparation B, and 1-acetyl-4-(4-hydroxyphenyl)piperazine (2.16 g.) dissolved in dry tetrahydrofuran (70 ml.), there was added triphenylphosphine (2.56 g.) and diethyl azodicarboxylate (1.71 g.) while under a dry nitrogen atmosphere. The reaction mixture was then stirred at room temperature (~20° C.) for a period of 20 hours. At the end of this time, further triphenylphosphine (1.28 g.) and diethyl azodicarboxylate (0.85 g.) were added to the mixture and stirring was continued for a further period of 20 hours. Upon completion of this step, the final reaction mixture was poured into methylene chloride (100 ml.) and extracted with N hydrochloric acid (three-50 ml. portions). The combined acidic extracts were then washed with methylene chloride (three-30 ml. portions) and subsequently basified to a pH value of 10 by the addition of 2 N aqueous sodium hydroxide with the aid of cooling in an ice bath. The basified aqueous solution was next extracted with methylene chloride (three-50 ml. portions), and the organic extracts were thereafter combined and subsequently dried over anhydrous magnesium sulfate. After removal of the drying agent, by means of filtration and the solvent by means of evaporation under reduced pressure, there was finally obtained a gum (4.87 g.) as residue. The latter material was subsequently chromatographed on silica, using methylene chloride (150 ml.) followed by a mixture of methylene chloride, isopropyl alcohol (2%) and concentrated ammonium hydroxide (0.2%) as the eluant. In this manner, there was obtained another gum as product and this was subsequently taken up in ethyl acetate and converted to the oxalate salt by the slow dropwise addition of a saturated solution of oxalic acid in diethyl ether until no further precipitation occurred. The resulting precipitate was then collected by means of suction filtration, washed with a little of diethyl ether and thereafter vacuum dried to afford the N-acetyl derivative of 2-(2,4-dichlorophenyl)-1-(imidazol-1-yl)-8-(4-piperazin-1-ylphenoxy)octan-2-ol as the dioxalate salt (yield, 6.7 g.), m.p. 75°-78° C.; Rf =0.3 (methylene chloride/isopropyl alcohol/ammonium hydroxide 90:10:1.0 by volume on silica); m/e, 558. The yield of pure product amounted to 90% of the theoretical value.

Workup

  1. stirringstirring
  2. waitwas continued for a further period of 20 hours
  3. customUpon completion of this step, the final reaction mixture
  4. extractionextracted with N hydrochloric acid (three-50 ml. portions)
  5. washThe combined acidic extracts were then washed with methylene chloride (three-30 ml. portions)
  6. additionsubsequently basified to a pH value of 10 by the addition of 2 N aqueous sodium hydroxide with the aid
  7. temperatureof cooling in an ice bath
  8. extractionnext extracted with methylene chloride (three-50 ml. portions)
  9. dry with materialsubsequently dried over anhydrous magnesium sulfate
  10. customAfter removal of the drying agent
  11. filtrationby means of filtration
  12. customthe solvent by means of evaporation under reduced pressure, there
  13. customwas finally obtained a gum (4.87 g.) as residue
  14. customThe latter material was subsequently chromatographed on silica
  15. additionfollowed by a mixture of methylene chloride, isopropyl alcohol (2%) and concentrated ammonium hydroxide (0.2%) as the eluant
  16. customIn this manner, there was obtained another gum as product
  17. filtrationThe resulting precipitate was then collected by means of suction filtration
  18. washwashed with a little of diethyl ether
  19. customvacuum dried

Sources & evidence

ORD record
ord-fb941ad2a262496886aee3588dfeaa3d
Source dataset
uspto-grants-1984_03
Patent number
US04435399

Reaction notes

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