Diisopropylamine → HCID 68748804, compound

HRID 333321Notes

Reaction equation

HRID 333321 reaction equation
C(NC(C)C)(C)C.[C:8]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])=[CH:10][CH:9]=1.Br[CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].[NH4+].[Cl-]>C1COCC1.[Li]CCCC>[C:8]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:13]=[CH:12][C:11]([CH2:14][CH:15]([CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 68753687Benzyl 3-(biphenyl-4-yl)propanoate

Product 1

HCID 68748804HCID 68748804, compoundYield 43.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418339ButyllithiumSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of diisopropylamine (2.70 ml, 18.96 mmol) in THF (20 ml), BuLi in hexanes (11.85 ml, 18.96 mmol) was added under nitrogen at 0° C. After stirred for 0.5 hour at the same temperature, the solution was cooled to −78° C. and then a solution of benzyl 3-(biphenyl-4-yl)propanoate (5 g, 15.80 mmol) in THF (20 ml) was added. After stirred for 1.5 hour at the same temperature, tert-butyl bromoacetate (3.33 ml, 22.12 mmol) was added, and then the mixture was warmed up to 0° C. The reaction mixture was allowed to stir at 0° C. for 2 hours, and then stirred at room temperature for 14 hours. The reaction mixture was poured into 150 ml of saturated aq. NH4Cl. The product was extracted twice with EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 10:1) to give the 1-benzyl 4-tert-butyl 2-(biphenyl-4-ylmethyl)succinate (2.97 g); Retention time=1.00 minutes (condition G); MS (m+1)=431.2.

Workup

  1. additionwas added
  2. temperaturethe mixture was warmed up to 0° C
  3. stirringto stir at 0° C. for 2 hours
  4. stirringstirred at room temperature for 14 hours
  5. extractionThe product was extracted twice with EtOAc
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 10:1)

Sources & evidence

ORD record
ord-3225caf2ccfa424a8edd721647ee650a
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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