Diisopropylamine → HCID 58460172, compound

HRID 1946528Notes

Reaction equation

HRID 1946528 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]1(=[O:20])[CH2:18][CH2:17][CH2:16][CH2:15][C:14]1=[O:19].Br[CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>CN1C2C(N=C(N)NC=2NCC1CNC1C=CC(C(NC(C(O)=O)CCC(O)=O)=O)=CC=1)=O>[C:27]1([CH2:26][O:25][C:23](=[O:24])[CH2:22][C:18]2[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=2[OH:20])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 130061,2-CyclohexanedioneHCID 62576Benzyl bromoacetateHCID 178418339Butyllithium

Product 1

HCID 58460172HCID 58460172, compound

Reagents, catalysts & solvents 1

HCID 178479889HCID 178479889, compoundSolvent2×

Conditions

Temperature
-10 °C

Procedure

A 1.6M solution of n-butyl lithium (81 mL, 130 mmol) was added to a stirred solution of diisopropylamine (18.26 mL) in methyl-THF (150 mL) at −10° C. The resulting solution was stirred at −10° C. for 15 mins. 1,2-cyclohexanedione (6.84 g) was added to the reaction mixture as a solution in methyl-THF (30 mL). During the addition the internal temperature of the reaction was maintained between −15° C. and −5° C. by modulation of delivery rate. The resulting dark orange/brown solution was stirred at −10 to −20° C. for a further 15 mins. The reaction mixture was then cooled to −50° C. and benzyl bromoacetate (12.62 mL, 79 mmol) was added dropwise via syringe. The mixture was stirred at this temperature for 10 minutes then aged at −78° C. for 1½ hours. The reaction mixture was quenched at −78° C. by dropwise addition of 1M HCl (300 ml). Ethyl acetate (200 mL) was added and the mixture allowed to warm to room temperature. The layers were separated and the organic phase washed with saturated brine (150 mL) and dried over sodium sulfate then reduced in vacuo. The resulting solid was purified by column chromatography, eluting with 0-25% ethyl acetate in cyclohexane. The appropriate fractions were reduced in vacuo to provide the product as a 1:1 mixture of thermodynamic enol:kinetic enol (registered as thermodynamic enol)

Workup

  1. additionDuring the addition the internal temperature of the reaction
  2. temperaturewas maintained between −15° C. and −5° C. by modulation of delivery rate
  3. stirringThe resulting dark orange/brown solution was stirred at −10 to −20° C. for a further 15 mins
  4. temperatureThe reaction mixture was then cooled to −50° C.
  5. stirringThe mixture was stirred at this temperature for 10 minutes
  6. waitthen aged at −78° C. for 1½ hours
  7. customThe reaction mixture was quenched at −78° C. by dropwise addition of 1M HCl (300 ml)
  8. additionEthyl acetate (200 mL) was added
  9. temperatureto warm to room temperature
  10. customThe layers were separated
  11. washthe organic phase washed with saturated brine (150 mL)
  12. dry with materialdried over sodium sulfate
  13. customThe resulting solid was purified by column chromatography
  14. washeluting with 0-25% ethyl acetate in cyclohexane
  15. customto provide the product

Sources & evidence

ORD record
ord-fceedbb8ef3244b18825b22f35dbc61b
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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