Diisopropylamine → HCID 53759594, compound

HRID 1377918Notes

Reaction equation

HRID 1377918 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:15][C:16](=[O:35])[CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[CH3:14].Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>C1COCC1>[C:41]([O:40][C:38](=[O:39])[CH2:37][CH:17]([C:16]([O:15][CH2:13][CH3:14])=[O:35])[CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][C:30]([C:33]#[N:34])=[CH:31][CH:32]=2)=[CH:23][CH:22]=1)([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 54147598HCID 54147598, compoundHCID 178418339Butyllithium

Product 1

HCID 53759594HCID 53759594, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a -78° C. solution in THF (100 mL) of diisopropylamine (0.94 mL, 7.15 mmol) was added n-butyllithium (25M in hexanes, 2.86 mL, 7. 15 mmol) and the mixture was stirred for 15 minutes. A solution in THF (25 mL) of 4-[4-(4-cyanophenyl)phenoxy]butanoic acid ethyl ester (2.01 g, 6.5 mmol), prepared as in step 1, was added dropwise and the reaction mixture was stirred for 15 minutes. Neat t-butyl bromoacetate (1.03 mL, 6.8 mmol) was added rapidly and the reaction mixture was stirred at -78° C. for 2 hours, then for 0.5 hours at ambient temperature. The reaction mixture was quenched with saturated aqueous NH4Cl and extracted twice with ethyl ether. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Successive chromatographies on silica gel (dichloromethane, then 1:3 ethyl acetate-hexanes) gave 3-carboethoxy-5-[4(4-cyanophenyl)phenoxy]pentanoic acid tert-butyl ester (0.91 g, 33%).

Workup

  1. additionwas added dropwise
  2. stirringthe reaction mixture was stirred for 15 minutes
  3. stirringthe reaction mixture was stirred at -78° C. for 2 hours
  4. waitfor 0.5 hours at ambient temperature
  5. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  6. extractionextracted twice with ethyl ether
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a8155d8e8374435ba327f9e57bcda0f
Source dataset
uspto-grants-1997_09
Patent number
US05665777

Reaction notes

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