Toluene → 3-(Benzhydrylidene-amino)-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one

HRID 2207642Notes

Reaction equation

HRID 2207642 reaction equation
[CH3:1][C:2](C)([O-])[CH3:3].[K+].[C:7](=[N:20][CH:21]1[CH2:25][CH2:24][N:23]([CH3:26])[C:22]1=[O:27])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(Br)C#C.C1(C)C=CC=CC=1>C1COCC1>[C:7](=[N:20][C:21]1([CH2:3][C:2]#[CH:1])[CH2:25][CH2:24][N:23]([CH3:26])[C:22]1=[O:27])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 23665647Potassium tert-butoxideHCID 896489983-(Benzhydrylidene-amino)-1-methyl-pyrrolidin-2-one

Product 1

HCID 896495353-(Benzhydrylidene-amino)-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

Potassium tert-butoxide 1.7M in THF (602.08 mL, 1023.5 mmol) was added dropwise over a period of 2.5 h to a stirred solution of 3-(benzhydrylidene-amino)-1-methyl-pyrrolidin-2-one (259 g, 930.48 mmol) (which may be prepared as described in Description 101) and 80% solution of propargyl bromide in toluene (124.37 mL, 1116.6 mmol) in 3 A-molecular-sieve-dried reagent grade THF (1900 mL) at −65° C. under nitrogen, in a 5 L flask equipped with an overhead stirrer. After the addition was complete, the mixture was stirred at −65° C. for a further 1 h. The cooling bath was removed and a saturated solution of NaHCO3 (140 ml) was added over 1 minute (at −60° C.). After a further 5 mins more sat NaHCO3 solution (1.4 L) was added followed by Et2O (1.4 L). The mixture was stirred for 1 h then transferred to a separating funnel and water (1.4 L) was added to dissolve all solids. The layers were separated and the aqueous further extracted with Et2O (2×1 L). The combined organic extracts were re-washed with sat. brine (700 ml), diluted with water (700 ml). The organic layer was dried (MgSO4) and evaporated to a volume of approx. 500-600 ml whereupon crystallization started to occur. To this stirred mixture was then added iso-hexane (1.6 L). After standing for 15 mins the cream solid was filtered under suction and washed with iso-hexane (500 ml) and dried at 50° C. under vacuum for 5 h. This afforded 3-(benzhydrylidene-amino)-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one (D102) (274 g, 93%). This was pure by NMR but contains some additional water;

Workup

  1. customequipped with an overhead stirrer
  2. additionAfter the addition
  3. customThe cooling bath was removed
  4. additiona saturated solution of NaHCO3 (140 ml) was added over 1 minute (at −60° C.)
  5. waitAfter a further 5 mins more sat
  6. additionNaHCO3 solution (1.4 L) was added
  7. stirringThe mixture was stirred for 1 h
  8. customthen transferred to a separating funnel
  9. additionwater (1.4 L) was added
  10. dissolutionto dissolve all solids
  11. customThe layers were separated
  12. extractionthe aqueous further extracted with Et2O (2×1 L)
  13. washThe combined organic extracts were re-washed with sat. brine (700 ml)
  14. additiondiluted with water (700 ml)
  15. dry with materialThe organic layer was dried (MgSO4)
  16. customevaporated to a volume of approx. 500-600 ml whereupon crystallization
  17. waitAfter standing for 15 mins
  18. filtrationthe cream solid was filtered under suction
  19. washwashed with iso-hexane (500 ml)
  20. customdried at 50° C. under vacuum for 5 h

Sources & evidence

ORD record
ord-ad2e96fee57741f9867eeb9a03d32c9b
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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