Dichloromethane → 4-(Chloromethyl)-2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl

HRID 1662329Notes

Reaction equation

HRID 1662329 reaction equation
[CH3:1][C:2]([C:5]1[CH:10]=[C:9]([CH2:11]O)[CH:8]=[CH:7][C:6]=1[C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[F:21])([CH3:4])[CH3:3].C(Cl)[Cl:23].S(Cl)(Cl)=O>>[Cl:23][CH2:11][C:9]1[CH:8]=[CH:7][C:6]([C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=2[F:21])=[C:5]([C:2]([CH3:4])([CH3:3])[CH3:1])[CH:10]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 24386Thionyl Chloride2×HCID 57705540(2-(1,1-Dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

Product 1

HCID 577056714-(Chloromethyl)-2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenylYield 74.3%

Procedure

To a cooled solution of 8.9 (0.56 g, 1.93 mmol) in dry DCM (3.60 mL, 1.93 mmol) at 0° C., was added thionyl chloride (0.40 mL, 5.48 mmol) dropwise. Upon complete addition of thionyl chloride, the mixture was allowed to warm to room temperature. After 18 hours, the reaction was concentrated in vacuo. The residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-15% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide 8.10 as a colorless solid (0.44 g, 74%). 1H NMR (500 MHz, CDCl3) δ ppm 7.56 (1H, s), 7.25 (5H, dd, J=7.7, 1.6 Hz), 7.01 (2H, m), 6.86 (1H, dd, J=9.0, 3.2 Hz), 6.77 (1H, dd, J=5.9, 3.2 Hz), 4.65 (3H, s), 3.79 (3H, s), 1.24 (9H, s).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customThe residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-15% EtOAc in hexanes)
  3. additionFractions containing the desired product
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3340c05a6c6a4733a9ab1306fa02728c
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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