Water → 1-Chloro-2-(2,4-difluorophenyl)-3-pivaloyloxybutan-2-ol

HRID 731012Notes

Reaction equation

HRID 731012 reaction equation
[Cl:1][CH2:2][C:3](=[O:13])[C@H:4]([O:6][C:7](=[O:12])[C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:5].[F:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[Mg]Br.[Cl-].[NH4+].O>C1(C)C=CC=CC=1>[Cl:1][CH2:2][C:3]([C:18]1[CH:17]=[CH:16][C:15]([F:14])=[CH:20][C:19]=1[F:21])([OH:13])[CH:4]([O:6][C:7](=[O:12])[C:8]([CH3:9])([CH3:11])[CH3:10])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 86606435HCID 86606435, compoundHCID 178505836HCID 178505836, compound

Product 1

HCID 231170411-Chloro-2-(2,4-difluorophenyl)-3-pivaloyloxybutan-2-olYield 71%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 0.41 g (2.0 mmol) of (R)-1-chloro-3-pivaloyloxybutan-2-one in 5 mL of toluene was cooled to 0° C., and 3.2 mL (2.2 mmol) of a 0.69 M solution of 2,4-difluorophenylmagnesium bromide prepared by the same method as that in Example 3 was added dropwise thereto over a period of 5 minutes. After the completion of the dropwise addition, stirring was continued for another 1 hour, and 10 mL of a saturated aqueous solution of ammonium chloride was added to stop the reaction. Furthermore, 10 mL of water was added, and extraction was performed with ethyl acetate (20 mL×2). After drying over anhydrous sodium sulfate, concentration was performed under reduced pressure to obtain 0.54 g of a crude product. The resulting product was purified by column on silica gel to obtain 0.450 g of the title compound (yield: 71%) ((2S,3R)/(2R,3R)=93/7 (the diastereomeric ratio was measured by HPLC under the same HPLC measurement conditions as those in Example 19)).

Workup

  1. additionwas added dropwise
  2. additionAfter the completion of the dropwise addition
  3. waitwas continued for another 1 hour
  4. customthe reaction
  5. extractionextraction
  6. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  7. customto obtain 0.54 g of a crude product
  8. customThe resulting product was purified by column on silica gel

Sources & evidence

ORD record
ord-8cb5a24fe6e1424bb23bb4d01262e7b5
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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