Ammonium Chloride → 1-Chloro-2-(2,5-difluorophenyl)-3-pivaloyloxybutan-2-ol

HRID 731020Notes

Reaction equation

HRID 731020 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[Mg]Br.FC1C=CC(F)=CC=1Br.[Mg].[Cl:21][CH2:22][C:23](=[O:33])[C@H:24]([O:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[CH3:25].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C(#N)C.O>[Cl:21][CH2:22][C:23]([C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[F:1])([OH:33])[CH:24]([O:26][C:27](=[O:32])[C:28]([CH3:30])([CH3:29])[CH3:31])[CH3:25]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 678622-Bromo-1,4-difluorobenzeneHCID 5462224MagnesiumHCID 86606435HCID 86606435, compoundHCID 178505813HCID 178505813, compound

Product 1

HCID 231170421-Chloro-2-(2,5-difluorophenyl)-3-pivaloyloxybutan-2-olYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,5-difluorophenylmagnesium bromide prepared from 5.79 g (30.0 mmol) of 2,5-difluorobromobenzene and 0.759 g (31.2 mmol) of magnesium by the same method as that in Example 3 was cooled to 0° C., and a solution of 3.10 g (15.0 mmol) of (R)-1-chloro-3-pivaloyloxybutan-2-one in 15 mL of toluene was added dropwise thereto. 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 63% ((2S,3R)/(2R,3R)=94/6) (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: 17.0 minutes (2S,3R), 13 minutes (2R,3R)). 1H-NMR (400 MHz, CDCl3) (2S,3R) δ: 1.07 (d, 3H, J=6.3 Hz), 1.24 (s, 9H), 3.86 (d, 1H, J=11.5 Hz), 4.20 (d, 1H, 11.5 Hz), 5.42 (q, 1H, J=6.3 Hz), 7.00-7.03 (m, 2H), 7.40-7.44 (m, 1H); (2R,3R) δ: 1.03 (s, 9H), 1.58 (d, 3H, J=6.3 Hz), 3.91 (d, 1H, J=11.5 Hz), 4.28 (d, 1H, 11.5 Hz), 5.31 (q, 1H, J=6.3 Hz), 6.99-7.02 (m, 2H), 7.26-7.37 (m, 1H).

Workup

  1. additionAfter the completion of the dropwise addition
  2. customthe reaction
  3. extractionextraction
  4. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  5. customto obtain a crude product

Sources & evidence

ORD record
ord-66098d58874346d9964291817c840178
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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