Ammonium Chloride → methyl (2R,3R)-2-(3,4-dichlorobenzyl)-3-hydroxybutyrate

HRID 376192Notes

Reaction equation

HRID 376192 reaction equation
[OH:1][C@H:2]([CH3:8])[CH2:3][C:4]([O:6][CH3:7])=[O:5].C([N-]C(C)C)(C)C.[Li+].[Cl:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[Cl:26])[CH2:21]Br.[Cl-].[NH4+]>O1CCCC1.O.C(OCC)C.CN(C)P(=O)(N(C)C)N(C)C.C1CCCCC1>[Cl:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[Cl:26])[CH2:21][C@H:3]([C@H:2]([OH:1])[CH3:8])[C:4]([O:6][CH3:7])=[O:5]

Participants

10

Reactant 4

HCID 25517Ammonium ChlorideHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 2724279Methyl 3-hydroxybutyrate, (R)-HCID 2724682Lithium diisopropylamide

Product 1

HCID 54181068methyl (2R,3R)-2-(3,4-dichlorobenzyl)-3-hydroxybutyrateYield 48%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-70 °C

Procedure

9.45 g of methyl (R)-(-)-3-hydroxybutyrate was dissolved in 200 ml of tetrahydrofuran, and 112 ml of a 1.5M cyclohexane solution of lithium diisopropylamide was added thereto with stirring under cooling to -70° C. Then, the temperature was raised to -25° C. Then, 35 ml of a hexamethylphosphoric triamide solution of 21.1 g of 3,4-dichlorobenzyl bromide was dropwise added to this solution under stirring while maintaining the temperature at -25° C. After the dropwise addition, the temperature was raised to room temperature. Then, a saturated ammonium chloride aqueous solution was added to the reaction solution with stirring under cooling with ice. Then, the temperature was raised to room temperature, and ethyl ether and water were added thereto for liquid separation. The organic layer was collected by separation and post-treated by a conventional method. The product was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to obtain 10.6 g (yield: 48%) of methyl (2R, 3R)-2-(3,4-dichlorobenzyl)-3-hydroxybutyrate.

Workup

  1. temperatureThen, the temperature was raised to -25° C
  2. stirringunder stirring
  3. temperaturewhile maintaining the temperature at -25° C
  4. additionAfter the dropwise addition
  5. temperaturethe temperature was raised to room temperature
  6. stirringwith stirring
  7. temperatureunder cooling with ice
  8. temperatureThen, the temperature was raised to room temperature
  9. customfor liquid separation
  10. customThe organic layer was collected by separation
  11. additionpost-treated by a conventional method
  12. customThe product was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-5bf4fd617c3947b79db07548dfc8823c
Source dataset
uspto-grants-1996_01
Patent number
US05488149

Reaction notes

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