Diisopropylamine → 3-(Cyclohexylamino)-1-(1-methyl-5-pyrrolidinyl)-2-butene-1-one

HRID 1721075Notes

Reaction equation

HRID 1721075 reaction equation
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[CH2:8]([Li])[CH2:9][CH2:10]C.CO[C:15](=[O:22])[C@@H:16]1[CH2:20][CH2:19][CH2:18][N:17]1[CH3:21]>C1COCC1>[CH:1]1([NH:4][C:5]([CH3:7])=[CH:6][C:15]([CH:16]2[N:17]([CH3:21])[CH2:18][CH2:19][CH2:20]2)=[O:22])[CH2:3][CH2:10][CH2:9][CH2:8][CH2:2]1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 10920622(S)-Methyl 1-methylpyrrolidine-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 677344693-(Cyclohexylamino)-1-(1-methyl-5-pyrrolidinyl)-2-butene-1-oneYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Diisopropylarnine (2.12 g, 21 mmol) and THF (35 mL) were added to a three-necked flask, which was flushed with N2. The solution was stirred with ice cooling, and n-butyllithium (1.6M in hexane, 12.5 mL, 20 mmol) was added dropwise over 20 min. To the resulting solution was added N-(1-methylethylidine)cyclohexanamine (prepared via the procedure of J. Org. Chem., 19:1054, 1954), over a 15 min period while maintaining the temperature at 0°±2° C., and the resulting solution was stirred at 0° C. for 20 min. To this solution was added 1.43 g (10.0 mmol) of N-methyl proline methyl ester over a 1 hr period, with stirring and cooling to maintain a temperature of 0°±2° C. The reaction was quenched by rapid addition of saturated aqueous ammonium chloride solution (10 mL). The layers were separated, and the aqueous layer was extracted one with 10 mL of ethyl acetate. The organic layers were combined and dried over Na2SO4. The solution was decanted from the solids and concentrated on a rotary evaporator to provide the product as a viscous oil (2.50 g). 1H NMR (CDCl3),δ:11.18 (br, 1H), 5.20 (s, 1H),3.40 (m, 1H), 2.62 (m, 1H), 2.33 (s, 3H), 2.21 (m, 1H), 1.97 (s, 3H), 1.9-1.5 (m, 8H), 1.5-1.0 (m, 6H), 13C NMR (CDCl3),δ:197.48 (s), 163.21 (s), 91.07 (d), 74.43 (d), 56.93 (t), 51.50 (d), 41.34 (q), 36.33 (t), 33.61 (t), 33.58 (t), 30.91 (t), 25.22 (t), 24.26 (t), 23.07 (t), 18.71 (q).

Workup

  1. customwhich was flushed with N2
  2. additionwas added dropwise over 20 min
  3. customprepared via the procedure of J
  4. temperature, 19:1054, 1954), over a 15 min period while maintaining the temperature at 0°±2° C.
  5. stirringwith stirring
  6. temperaturecooling
  7. temperatureto maintain a temperature of 0°±2° C
  8. customThe reaction was quenched by rapid addition of saturated aqueous ammonium chloride solution (10 mL)
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted one with 10 mL of ethyl acetate
  11. dry with materialdried over Na2SO4
  12. customThe solution was decanted from the solids
  13. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-37c1241d29cb4c61b8d95660b9245bc3
Source dataset
uspto-grants-1996_04
Patent number
US05508418

Reaction notes

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