Thionyl Chloride → 4-(Chloromethyl)-5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl

HRID 1662443Notes

Reaction equation

HRID 1662443 reaction equation
[F:1][CH:2]([F:25])[C:3]1[CH:4]=[CH:5][C:6]([F:24])=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][C:10]=2[C:17]2[C:21]([CH3:23])([CH3:22])[CH2:20][CH2:19][CH:18]=2)[CH:8]=1.S(Cl)([Cl:28])=O>C(Cl)Cl.CN(C=O)C>[Cl:28][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:7]2[CH:8]=[C:3]([CH:2]([F:25])[F:1])[CH:4]=[CH:5][C:6]=2[F:24])=[C:10]([C:17]2[C:21]([CH3:23])([CH3:22])[CH2:20][CH2:19][CH:18]=2)[CH:11]=1

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 57706435(5'-(Difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-yl)methanol

Product 1

HCID 577064584-(Chloromethyl)-5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenylYield 98.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 66.50C (0.1666 g, 0.481 mmol) in dry DCM (3 mL) and dry DMF (0.06 mL) was added thionyl chloride (0.07 mL, 0.96 mmol) at 0° C. The resulting solution was warmed to room temperature and monitored with TLC and LCMS. After 45 minutes, the reaction was concentrated and then purified by silica gel flash chromatography (0-5% EtOAc/hexane) to afford 66.50D (172.1 mg, 98% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.46 (2H, m), 7.39 (1H, m), 7.33 (1H, m), 7.28 (1H, d, J=1.7 Hz), 7.17 (1H, m), 6.62 (1H, t), 5.51 (1H, td, J=2.3, 1.0 Hz), 4.64 (2H, s), 2.24 (2H, td, J=7.1, 2.4 Hz), 1.68 (2H, m), 0.85 (6H, s).

Workup

  1. concentrationthe reaction was concentrated
  2. custompurified by silica gel flash chromatography (0-5% EtOAc/hexane)

Sources & evidence

ORD record
ord-33ec2389903a45bdbef6e87974876934
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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