Diethyl Ether → HCID 20080505, compound

HRID 1653819Notes

Reaction equation

HRID 1653819 reaction equation
C1(NC2CCCCC2)CCCCC1.[C:14]([CH:16]([CH3:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=O)#[N:15].S([O-])(O)(=O)=O.[Na+].C(OCC)C.Cl.[NH2:38][CH:39]([C:50]1[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=1)[C:40]([C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1)=[O:41]>ClCCl.O.N1C=CC=CC=1>[CH3:49][O:48][C:45]1[CH:46]=[CH:47][C:42]([C:40](=[O:41])[CH:39]([C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)[NH:38][C:22](=[O:24])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([C:14]#[N:15])[CH3:25])=[CH:43][CH:44]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516919Sodium BisulfateHCID 200805132-Amino-1,2-bis(4-methoxyphenyl)ethan-1-one--hydrogen chloride (1/1)HCID 67784761HCID 67784761, compound

Product 1

HCID 20080505HCID 20080505, compoundYield 83.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

14.4 g of 7-cyanooctanoic acid dicyclohexylamine salt are added to a mixture of 45 cm3 of a molar solution of sodium hydrogen sulphate and 100 cm3 of diethyl ether. The mixture is stirred for 15 minutes at 20° C. and the organic phase is then separated. The latter is dried over magnesium sulphate and filtered and the solvent is evaporated off under reduced pressure. The residue, treated with 24.6 g of thionyl chloride is heated to 50° C. for 3 hours. The mixture is evaporated under reduced pressure. The residual oil is dissolved in 10 cm3 of dichloromethane, and the solution obtained is added to a suspension, stirred and cooled to 5° C., of 12.1 g of 2-amino-1,2-bis(4-methoxyphenyl)ethanone hydrochloride in 50 cm3 of dichloromethane containing 7.8 g of pyridine. The mixture is stirred for 20 hours at room temperature, 40 cm3 of water are then added and the organic phase is separated after settling has taken place and washed with 20 cm3 of normal hydrochloric acid and with water (3 times 20 cm3). The organic phase is dried over magnesium sulphate and filtered and the solvent is evaporated off under reduced pressure. The residue is chromatographed on a column 2.8 cm in diameter containing 100 g of silica gel (50 to 200μ). The column is eluted, collecting 200 cm3 fractions, with 4 liters of a diisopropyl ether/ethyl acetate (80:20 by volume) mixture. The fractions emerging at between 0.6 liter and 4 liters are concentrated under reduced pressure (0.2 kPa). 13.9 g (83%) of (RS)-1,2-bis(4-methoxyphenyl)-2-(7-cyanooctanamido)ethanone are obtained in the form of a yellowish oil, which is used directly in the subsequent reaction.

Workup

  1. customthe organic phase is then separated
  2. dry with materialThe latter is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is evaporated off under reduced pressure
  5. additionThe residue, treated with 24.6 g of thionyl chloride
  6. temperatureis heated to 50° C. for 3 hours
  7. customThe mixture is evaporated under reduced pressure
  8. dissolutionThe residual oil is dissolved in 10 cm3 of dichloromethane
  9. customthe solution obtained
  10. additionis added to a suspension
  11. stirringstirred
  12. stirringThe mixture is stirred for 20 hours at room temperature
  13. customthe organic phase is separated after settling
  14. washwashed with 20 cm3 of normal hydrochloric acid and with water (3 times 20 cm3)
  15. dry with materialThe organic phase is dried over magnesium sulphate
  16. filtrationfiltered
  17. customthe solvent is evaporated off under reduced pressure
  18. customThe residue is chromatographed on a column 2.8 cm in diameter
  19. additioncontaining 100 g of silica gel (50 to 200μ)
  20. washThe column is eluted
  21. customcollecting 200 cm3 fractions
  22. concentrationare concentrated under reduced pressure (0.2 kPa)

Sources & evidence

ORD record
ord-d0d7a60d253c415d96e9d39d627a4fe4
Source dataset
uspto-grants-1995_04
Patent number
US05403852

Reaction notes

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