Diisopropylamine → HCID 19384700, compound

HRID 2399773Notes

Reaction equation

HRID 2399773 reaction equation
[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.C([Li])CCC.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]([CH3:34])[C:29]([O:31]CC)=[O:30])=[CH:24][CH:23]=1.[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=1)[CH2:39]Cl.[OH-].[Na+]>C1COCC1.CCCCCC.C(O)C>[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=1)[CH2:39][C:28]([C:25]1[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][CH:26]=1)([CH3:34])[C:29]([OH:31])=[O:30]

Participants

10

Reactant 6

HCID 7912DiisopropylamineHCID 12103m,alpha-DichlorotolueneHCID 14798Sodium HydroxideHCID 2724682Lithium diisopropylamideHCID 10867613HCID 10867613, compoundHCID 178418339Butyllithium

Product 1

HCID 19384700HCID 19384700, compoundYield 91.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of LDA in THF (1 liter), which had been prepared from diisopropylamine (35 g) and a 1.6M solution of n-butyl lithium in hexane (216 ml), was added dropwise a solution of ethyl 2-(4-chlorophenyl)propionate (70 g) in THF (100 ml) which had been obtained in paragraph 1), at a temperature of -45° to -40° C. under an atmosphere of nitrogen gas. At the same temperature, the reaction mixture was stirred for 0.5 hours, and m-chlorobenzyl chloride (55.7 g) was added dropwise thereto. The mixture was subjected to the same post-treatment as described in paragraph 1), and the residue was dissolved in ethanol (700 ml). To this solution was added dropwise 40% aqueous sodium hydroxide (40 ml), followed by heating under reflux for 5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was added dropwise to 10% aqueous hydrochloric acid under ice-cooling, and extracted several times with dichloromethane. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting crystalline residue was washed with hexane to give 2 -(3-chlorobenzyl)-2-(4-chlorophenyl)propionic acid (yield, 93 g) as white crystals, m.p., 154.8° C.

Workup

  1. customhad been obtained in paragraph 1), at a temperature of -45° to -40° C. under an atmosphere of nitrogen gas
  2. temperatureby heating
  3. temperatureunder reflux for 5 hours
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. additionThe resulting residue was added dropwise to 10% aqueous hydrochloric acid under ice-
  6. temperaturecooling
  7. extractionextracted several times with dichloromethane
  8. dry with materialThe extract was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. washThe resulting crystalline residue was washed with hexane

Sources & evidence

ORD record
ord-2a2fbc3d923f49d6919f14fbe429e2cc
Source dataset
uspto-grants-1995_09
Patent number
US05451607

Reaction notes

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