Diisopropylamine → Lithium diisopropylamide

HRID 2049328Notes

Reaction equation

HRID 2049328 reaction equation
[CH2:1]([Li:5])[CH2:2][CH2:3]C.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[OH:13][C:14]1[CH:15]=[C:16]([CH:20]2[CH2:24][CH2:23][N:22]([CH3:25])[C:21]2=[O:26])[CH:17]=[CH:18][CH:19]=1.ICCC>C1COCC1.O>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:5].[OH:13][C:14]1[CH:15]=[C:16]([C:20]2([CH2:1][CH2:2][CH3:3])[CH2:24][CH2:23][N:22]([CH3:25])[C:21]2=[O:26])[CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 336431-IodopropaneHCID 12665519HCID 12665519, compoundHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 12926607HCID 12926607, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium diisopropylamide was prepared under nitrogen at room temperature from n-butyllithium (1.4 M in hexane, 16 ml) and diisopropylamine (2.8 ml, 2.02 g). A solution of 3-(3-hydroxyphenyl)-1-methyl-2-pyrrolidone (1.71 g) in THF (50 ml) was added and the resulting suspension was stirred for 1 hour at room temperature. 1-Iodopropane (0.95 ml, 1.63 g) was then added in one lot, when the acid immediately dissolved. The mixture was warmed over 2 hours to reflux, held at reflux for 30 minutes, cooled, and treated with water (20 ml). Organic solvents were removed under reduced pressure and the residual aqueous phase was diluted with water (20 ml), and extracted with dichloromethane (2×50 ml). The lower emulsion phases were separated, combined, and back-extracted with water (3×10 ml). The dichloromethane phase was dried (MgSO4) and evaporated, leaving impure title compound as a brown gum which partially crystallised (0.3 g). The aqueous phases were combined with the original aqueous phase (pH>12) and acidified with conc. hydrochloric acid to pH<1. The precipitated yellow gum was extracted into dichloromethane (4×25 ml) and the combined extracts were dried (MgSO4) and evaporated, leaving a brown gum which crystallised on trituration with a little ethyl acetate (2.04 g). This material was crystallised, after charcoal treatment in ethyl acetate and removal of the solvent, from cyclohexane-toluene (about 1:1 v/v) to give 3-(3-hydroxyphenyl)-1-methyl-3-(1-propyl)-2-pyrrolidone as ochre crystals (0.91 g), m.p. 75.5°-76.5° C.

Workup

  1. dissolutionimmediately dissolved
  2. temperatureThe mixture was warmed over 2 hours
  3. temperatureto reflux
  4. temperatureat reflux for 30 minutes
  5. temperaturecooled
  6. customOrganic solvents were removed under reduced pressure
  7. additionthe residual aqueous phase was diluted with water (20 ml)
  8. extractionextracted with dichloromethane (2×50 ml)
  9. customThe lower emulsion phases were separated
  10. extractionback-extracted with water (3×10 ml)
  11. dry with materialThe dichloromethane phase was dried (MgSO4)
  12. customevaporated

Sources & evidence

ORD record
ord-a56ce06cbf534a3f8df48f9db60095e1
Source dataset
uspto-grants-1980_04
Patent number
US04197241

Reaction notes

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