Ethanol → HCID 131717469, compound

HRID 654598Notes

Reaction equation

HRID 654598 reaction equation
[C:1](=[O:4])([O-])[O-:2].[K+].[K+].[CH:7]1([NH2:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.Br[CH2:15][CH2:16][CH2:17][C:18]([O:20]CC)=O.[O-][CH2:24][CH3:25].[Na+].[CH2:27]([OH:29])C>C(Cl)Cl>[CH:7]1([N:13]2[CH2:15][CH2:16][CH:17]([C:1]([O:2][CH2:24][CH3:25])=[O:4])[C:18](=[O:20])[C:27]2=[O:29])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

7

Reactant 5

HCID 702EthanolHCID 7965CyclohexylamineHCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 2723922Sodium ethoxide

Product 1

HCID 131717469HCID 131717469, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of potassium carbonate (9.65 g, 69.9 mmole) in cyclohexylamine (8.0 mL, 69.9 mmole) was added ethyl 4-bromobutyrate (10.0 mL, 69.9 mmole) and the mixture was stirred at room temperature for 24 hours. The resulting solid mass was dissolved in methylene chloride (100 mL) and washed with water (100 mL). Evaporation of the organic phase under vacuum left a turbid oil which was dissolved again in methylene chloride (100 mL) and to it added 1 N aq. NaOH (100 mL). While cooling the mixture in a cold water bath, ethyl oxalyl chloride (7.8 mL, 70 mmole) was added and the reaction was stirred for 15 minutes. The methylene chloride layer was separated, dried over MgSO4, and evaporated under vacuum, leaving an amber oil. This was dissolved ini absolute ethanol (50 mL) and to it added a solution of ethanolic sodium ethoxide (21 wt.%, 26 mL, 70 mmole). The solution was refluxed on a steam bath for 1.5 hours, cooled and then most of the solvent removed under vacuum. The resulting tan chunky solid was suspended in water (250 mL) which had been made acidic with concentrated HCl (5 mL) and stirred vigorously at room temperature overnight, turning into a flocculent, lighter colored solid. This was collected by suction filtration, washed with water, and air dried. Crystallization from 1/1 ethanol/water (100 mL) gave, after cooling to 0° C., gave the subtitled ester, 1.80 g (15%) of light tan needles (m.p. 88°-89°). A second crop from 50 mL of the same solvent gave an additional 0.55 g of the ester for a total yield of 3.35 g (18%). 1H NMR (CDCl3, δ) 4.3 (m, 1H, NC-H), 4.25 (q, 2H, J= 7 Hz, OCH2), 3.30 (t, 2H, J=7 Hz, NCH2), 2.46 (t, 2H, J=7 Hz, NCH2CH2), 1.30 (t, 3H, J=7 Hz, CH3), 1.1-1.9 (m, 10H); IR (mull) 1658, 1613, 1242, 1226 cm-1 ; UV (ethanol) λmax (68 ) 251 (8180), 290(6730); MS m/e (rel. intens.) 267 (m+, 34), 221 (25), 193 (31), 186 (25), 150 (17), 140 (100); Exact mass calc'd for C14H21NO4 =267.1470; Found=267.1461; TLC (silica, 10% methanol/chloroform) Rf 0.7.

Workup

  1. washwashed with water (100 mL)
  2. customEvaporation of the organic phase under vacuum
  3. waitleft a turbid oil which
  4. dissolutionwas dissolved again in methylene chloride (100 mL) and to it
  5. additionadded 1 N aq. NaOH (100 mL)
  6. temperatureWhile cooling the mixture in a cold water bath
  7. stirringthe reaction was stirred for 15 minutes
  8. customThe methylene chloride layer was separated
  9. dry with materialdried over MgSO4
  10. customevaporated under vacuum
  11. customleaving an amber oil
  12. temperatureThe solution was refluxed on a steam bath for 1.5 hours
  13. temperaturecooled
  14. custommost of the solvent removed under vacuum
  15. stirringstirred vigorously at room temperature overnight
  16. filtrationThis was collected by suction filtration
  17. washwashed with water, and air
  18. customdried
  19. customCrystallization from 1/1 ethanol/water (100 mL)
  20. customgave
  21. temperatureafter cooling to 0° C.

Sources & evidence

ORD record
ord-63f06165b4f540228c0a8f4435effcfb
Source dataset
uspto-grants-1992_07
Patent number
US05132424

Reaction notes

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