Hydrochloric Acid → HCID 54135301, compound

HRID 568965Notes

Reaction equation

HRID 568965 reaction equation
[CH:1](=[N:8][C:9](=[CH:15][CH2:16][CH2:17][CH3:18])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.CCN(CC)CC.C(Cl)(=[O:34])C1C=CC=CC=1>C1COCC1.C(Cl)Cl>[CH2:13]([O:12][C:10](=[O:11])[C:9]([NH:8][C:1](=[O:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[CH:15][CH2:16][CH2:17][CH3:18])[CH3:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 54050285HCID 54050285, compound

Product 1

HCID 54135301HCID 54135301, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Schiff base (6) (97.1 g, 0.4M) is dissolved in THF (250 ml) and shaken in a separatory funnel with 10% aqueous HCl (1 l) for 5 minutes. This mixture is washed with Et2O (3×250 ml), the aqueous phase separated, neutralized with solid NaHCO3 and extracted with CHCl3 (3×250 ml). The combined CHCl3 extracts are dried over anhydrous MgSO4, filtered and evaporated to yield a pale yellow liquid, 57.9 g (93% yield). 'H-N.M.R. (CDCl3 /TMS): δ=1.30 (t, 3H, --CH2CH3); 1.50 (s, 2H, --NH2); 1.47-2.38 (m, 4H, --CH2CH2 --); 3.43 (dd, 1H, >CH--CH2 --, J=6 and 8 Hz); 4.20 (q, 2H, --CH2CH3); 4.80-5.20 (m, 2H, --CH=CH2); 5.45-6.20 ppm (m, 1H, --CH=CH2). The latter is stirred in CH2Cl2 (600 ml) containing Et3N (51 ml, 0.37M) and cooled in an ice bath before benzoyl chloride (43 ml, 0.37M) in CH2Cl2 (100 ml) is added dropwise over a period of 1/2 hour. The reaction mixture is allowed to warm to room temperature and stirred overnight. The formed Et3N HCl is removed by filtration and the filtrate is evaporated to dryness. The residue is taken up in Et2O, filtered, washed with 5% aqueous HCl (3×100 ml), saturated aqueous NaHCO3 (3×100 ml), saturated aqueous NaCl (3×100 ml), dried over anhydrous MgSO4 and evaporated to dryness. The white solid thus obtained is recrystallized twice from Et2O/hexane to yield 64.3 g of the desired product (7) (67% yield) m.p. 68°-70° C. The two recrystallizations are required in order to remove an impurity which turned out to be the bis alkylated material (m.p. 46°-49° C.) that is carried along. 'H-N.M.R. (CDCl3 /TMS): δ=1.3 (t, 3H, --CH2CH3); 1.80-2.34 (m, 4H, --CH2CH2 --); 4.28 (q, 2H, --CH2CH3); 4.64-5.15 (m, 3H, >CH=CH2 and CHCO2Et); 5.53-6.0 (m, 1H, CHCH2); 6.70 (d, 1H, >NH); 7.30-7.85 ppm (m, 5H, Ph).

Workup

  1. washThis mixture is washed with Et2O (3×250 ml)
  2. customthe aqueous phase separated
  3. extractionextracted with CHCl3 (3×250 ml)
  4. dry with materialThe combined CHCl3 extracts are dried over anhydrous MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a pale yellow liquid, 57.9 g (93% yield)
  8. additionis added dropwise over a period of 1/2 hour
  9. customThe formed Et3N HCl is removed by filtration
  10. customthe filtrate is evaporated to dryness
  11. filtrationfiltered
  12. washwashed with 5% aqueous HCl (3×100 ml), saturated aqueous NaHCO3 (3×100 ml), saturated aqueous NaCl (3×100 ml)
  13. dry with materialdried over anhydrous MgSO4
  14. customevaporated to dryness
  15. customThe white solid thus obtained
  16. customis recrystallized twice from Et2O/hexane

Sources & evidence

ORD record
ord-847a4491d4914dfcb31d3f41706daf88
Source dataset
uspto-grants-1988_03
Patent number
US04730006

Reaction notes

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