Thionyl Chloride → 3-(Chloromethyl)-2-cyclopropyl-6-(trifluoromethyl)pyridine

HRID 2101404Notes

Reaction equation

HRID 2101404 reaction equation
[CH:1]1([C:4]2[C:9]([CH2:10]O)=[CH:8][CH:7]=[C:6]([C:12]([F:15])([F:14])[F:13])[N:5]=2)[CH2:3][CH2:2]1.S(Cl)([Cl:18])=O>ClCCl.CN(C=O)C.CCOC(C)=O>[Cl:18][CH2:10][C:9]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:5][C:6]([C:12]([F:15])([F:14])[F:13])=[CH:7][CH:8]=1

Participants

6

Reactant 2

HCID 24386Thionyl ChlorideHCID 59834793(2-Cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)methanol

Product 1

HCID 598347923-(Chloromethyl)-2-cyclopropyl-6-(trifluoromethyl)pyridineYield 93.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of (2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)methanol (890 mg, 4.1 mmol) in dichloromethane (10 mL) at room temperature under argon was added thionyl chloride (730 mg, 6.1 mmol) followed by 3 drops of DMF. The reaction mixture was stirred at room temperature for 15 h. The reaction mixture was then concentrated under vacuum to obtain a light brown oil. This oil was diluted with EtOAc (20 mL) and washed with 10% aqueous Na2CO3 solution (20 mL). The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated to obtain 900 mg of the title compound as a light brown oil. HPLC/MS: retention time=3.66 min, [M+H]+=236.

Workup

  1. concentrationThe reaction mixture was then concentrated under vacuum
  2. customto obtain a light brown oil
  3. washwashed with 10% aqueous Na2CO3 solution (20 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4062294ab27045e0b02735fe7c795775
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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