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

HRID 731011Notes

Reaction equation

HRID 731011 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>C1COCC1.C(#N)C>[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

7

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 15%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.41 g (2.0 mmol) of (R)-1-chloro-3-pivaloyloxybutan-2-one in 5 mL of THF 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 a crude product. A quantitative analysis was performed by HPLC. Thereby, the title compound was obtained in a yield of 15% ((2S,3R)/(2R,3R)=92/8) (HPLC, column: YMC-A302 manufactured by YMC Co. Ltd., mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=6/4, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 10 minutes (2S,3R) and 8 minutes (2R,3R)). 1H-NMR (400 MHz, CDCl3) δ: 1.05 (d, 3H, J=6.3 Hz), 1.25 (s, 9H), 3.86 (d, 1H, J=11.5 Hz), 4.19 (d, 1H, 11.5 Hz), 5.38 (q, 1H, J=6.3 Hz), 6.77-6.80 (m, 1H), 6.91-6.93 (m, 1H), 7.69-7.71 (m, 1H).

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 a crude product

Sources & evidence

ORD record
ord-ad626fb911cd49819ccad94e2f128760
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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