Ethyl bromoacetate → HCID 58460212, compound

HRID 1946508Notes

Reaction equation

HRID 1946508 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][CH3:27])=[O:24]>CN1C2C(N=C(N)NC=2NCC1CNC1C=CC(C(NC(C(O)=O)CCC(O)=O)=O)=CC=1)=O>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][C:18]1[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=1[OH:20])[CH3:27]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetate2×HCID 7912DiisopropylamineHCID 130061,2-CyclohexanedioneHCID 178418339Butyllithium

Product 1

HCID 58460212HCID 58460212, compound

Reagents, catalysts & solvents 1

HCID 178479889HCID 178479889, compoundSolvent2×

Conditions

Temperature
-10 °C

Procedure

n-Butyl lithium (101 mL, 161 mmol) was added to a stirred solution of diisopropylamine (22.96 mL) in methyl-THF (200 mL) at −10° C. The resulting solution was stirred at −10° C. for 15 mins. 1,2-cyclohexanedione (8.6 g) was added to the reaction mixture as a solution in methyl-THF (28 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° C. for a further 15 mins. The reaction mixture was then cooled to −78° C. and ethyl bromoacetate (12.76 mL) was added dropwise via syringe. Further ethyl bromoacetate (0.8 mL) was added, no further evolution of heat was observed therefore the reaction was left to stir at −60 to −70° C. (internal temp) for 1 hour 15 minutes. The reaction mixture was quenched at −78° C. with 0.5 M HCl (400 ml), allowed to warm to RT and extracted with diethyl ether (200 ml). The organic layer was washed with water (300 mL) and saturated brine. The crude reaction mixture was purified by flash column chromatography (100 g, silica, ethyl acetate/cyclohexane, 0-50%) to give the title compound (7.1 g). LC/MS MH+ 199, Rt 1.78 mins (5 min system).

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° C. for a further 15 mins
  4. temperatureThe reaction mixture was then cooled to −78° C.
  5. temperatureno further evolution of heat
  6. waitthe reaction was left
  7. stirringto stir at −60 to −70° C. (internal temp) for 1 hour 15 minutes
  8. customThe reaction mixture was quenched at −78° C. with 0.5 M HCl (400 ml)
  9. temperatureto warm to RT
  10. extractionextracted with diethyl ether (200 ml)
  11. washThe organic layer was washed with water (300 mL) and saturated brine
  12. customThe crude reaction mixture
  13. customwas purified by flash column chromatography (100 g, silica, ethyl acetate/cyclohexane, 0-50%)

Sources & evidence

ORD record
ord-236262912a2d4987b584602d16190feb
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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