Water → 1-Chloro-2-(2,4-difluorophenyl)-3-(tert-butyldimethylsilyloxy)butan-2-ol

HRID 731005Notes

Reaction equation

HRID 731005 reaction equation
[Cl:1][CH2:2][C:3](=[O:14])[C@@H:4]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])[CH3:5].[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[Mg]Br.[Cl-].[NH4+].O>C1(C)C=CC=CC=1>[Cl:1][CH2:2][C:3]([C:19]1[CH:18]=[CH:17][C:16]([F:15])=[CH:21][C:20]=1[F:22])([OH:14])[CH:4]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:8])[CH3:9])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 10889936(S)-1-Chloro-3-(tert-butyldimethylsilyloxy)butan-2-oneHCID 178505836HCID 178505836, compound

Product 1

HCID 231170471-Chloro-2-(2,4-difluorophenyl)-3-(tert-butyldimethylsilyloxy)butan-2-olYield 91%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 0.69 g (3.0 mmol) of (S)-1-chloro-3-(tert-butyldimethylsilyloxy)butan-2-one in 5 mL of toluene was cooled to −20° C., and 5.3 mL (3.3 mmol) of a solution of 2,4-difluorophenylmagnesium bromide prepared by the same method as that in Example 3 was added dropwise thereto over a period of 15 minutes. After the completion of the dropwise addition, stirring was continued for another 2 hours, 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 colorless oil. A quantitative analysis was performed by HPLC (under the same HPLC measurement conditions as those in Example 3). Thereby, the title compound was obtained in a yield of 91% (2R,3S)/(2S,3S)=92/8). 1H-NMR (400 MHz, CDCl3) (2R,3S) δ: 0.10 (s, 6H), 0.92 (s, 12H), 3.85 (d, 1H, J=12.0 Hz), 4.07 (d, 1H, J=12.0 Hz), 4.35 (q, 1H, J=6.6 Hz), 6.77-6.79 (m, 1H), 6.93-6.93 (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 2 hours
  4. customthe reaction
  5. extractionextraction
  6. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  7. customto obtain a colorless oil

Sources & evidence

ORD record
ord-6141ba4234b04840a4148503706cf6ff
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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