Ethyl bromoacetate → HCID 10082877, compound

HRID 483390Notes

Reaction equation

HRID 483390 reaction equation
[C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:8]1C[CH2:11][CH2:10][CH2:9]1.C(#N)C=C.Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20]>C1C=CC=CC=1>[C:9]([CH2:10][CH2:11][CH:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:1]1=[O:7])#[N:8]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 7855AcrylonitrileHCID 7967CyclohexanoneHCID 31268Pyrrolidine

Product 1

HCID 10082877HCID 10082877, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

An oven dried 250 ml 1-necked round bottomed flask was charged with cyclohexanone (26.37 g, 0.27 mol) and dry benzene (50 ml). To this solution was added pyrrolidine (29 ml, 0.35 mol) over 10 min through a dropping funnel. The resultant solution was refluxed for 3 hours with azeotroping off water and then concentrated by distilling off benzene. The remaining crude enamine was dissolved in p-dioxane (100 ml) and treated with acrylonitrile (20 ml, 0.3 mol) and refluxed for 6 hours, and then slowly treated with ethyl bromoacetate (31 ml, 0.28 mol), and refluxed for further 12 hours. Then the reaction mixture was concentrated under reduced pressure, and treated with water (30 ml) and 10% sulfuric acid (50 ml) at room temperature. The resultant solution was diluted with ether (200 ml). The organic layer was separated from the aqueous layer and further extracted twice with ether (100 ml×2), combined, and washed with saturated NaCl solution (200 ml). The resulting organic layer was dried over anhydrous magnesium sulfate, and filtered, and the solvent was removed at reduced pressure to yield a crude product. Vacuum distillation at 0.1 torr afforded the desired product 2 (37.10 g, 58%) as a mixture of cis and trans stereoisomers: bp 160°-175° C. (0.1 torr); FT-IR (neat, cm-1) 2936, 2861, 2245, 1732, 1710, 1449, 1376, 1344, 1276, 1234, 1188, 1116, 1071, 1028, 989, 947, 862, 838, 748; 1H NMR (CDCl3, 400 MHz) δ 4.14 (q, J=7.1 Hz, 2H), 2.92 (m, 1H), 2.75 (dd, 16.6, 7.2 Hz, 1H), 2.56 (m, 1H), 2.45 (t, J=7.4 Hz, 1H), 2.43 (t, J=7.5 Hz, 1H), 2.17 (dd, J=16.6, 5.7 Hz, 2H), 2.22-2.05 (m, 2H), 1.96-1.78 (m, 2H), 1.55 (ddd, J=17.4, 8.8, 4.7 Hz, 1H), 1.42 (m, 2H), 1.26 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 210.92, 172.22, 119.63, 48.92, 48.81, 47.35 (47.14 for minor), 34.80, 34.55, 34.25, 34.13, 4.93, 15.09 (14.07 for minor); MS (El, 70 eV, rel. intensity) 237 (M, 17), 208(12), 192(B), 191(59), 163(27), 150(58), 141(35), 95(20), 84(27), 67(13), 55(20), 49(14); HRMS (El) calcd. for C13H19NO3 237.1365. Found 237.1361.

Workup

  1. customAn oven dried 250 ml 1-necked round bottomed flask
  2. customwith azeotroping off water
  3. concentrationconcentrated
  4. distillationby distilling off benzene
  5. dissolutionThe remaining crude enamine was dissolved in p-dioxane (100 ml)
  6. temperaturerefluxed for 6 hours
  7. temperaturerefluxed for further 12 hours
  8. concentrationThen the reaction mixture was concentrated under reduced pressure
  9. additiontreated with water (30 ml) and 10% sulfuric acid (50 ml) at room temperature
  10. additionThe resultant solution was diluted with ether (200 ml)
  11. customThe organic layer was separated from the aqueous layer
  12. extractionfurther extracted twice with ether (100 ml×2)
  13. washwashed with saturated NaCl solution (200 ml)
  14. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. customthe solvent was removed at reduced pressure
  17. customto yield a crude product
  18. distillationVacuum distillation at 0.1 torr

Sources & evidence

ORD record
ord-2c9798ce211349d983e78ebe4c11cf75
Source dataset
uspto-grants-1993_07
Patent number
US05225437

Reaction notes

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