Pyridine → HCID 68542521, compound

HRID 1446715Notes

Reaction equation

HRID 1446715 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=1.N1C=CC=CC=1>ClCCl.CC=C(C)C.C(#N)C1C=CC=CC=1.C(Cl)(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([C:27]([F:28])([F:29])[F:30])[CH:20]=2)=[O:11])=[CH:6][CH:7]=1

Participants

10

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 74654Benzeneacetic acid, 4-bromo-HCID 5221704-Amino-2-(trifluoromethyl)benzonitrile

Product 1

HCID 68542521HCID 68542521, compoundYield 48.5%

Reagents, catalysts & solvents 5

HCID 6212ChloroformSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 7505BenzonitrileSolventHCID 105532-Methyl-2-buteneSolvent2×

Procedure

Dissolve 4-bromo-phenyl acetic acid (5 g, 23.3 mmol) in 125 mL dichloromethane. Add 1 mL DMF, stir to give a clear solution, then add oxalyl chloride (3.25 g, 2.23 mL, 25.5 mmol) portionwise via syringe and stir at room temperature for 15-30 minutes until gas evolution ceases. Remove volatiles on rotovap to yield a clear yellow oil. Dissolve the oil in 100 mL amylene-stabilized chloroform, chill on ice and fit flask with a dropping funnel. Fill the dropping funnel with a solution of 4-amino-2-trifluoromethyl-benzonitrile (4.65 g, 25 mmol) and pyridine (6.05 g, 6.19 mL, 76.5 mmol) in 200 mL amylene-stabilized chloroform. Add the benzonitrile solution to the cold acid chloride solution with stirring over 30 minutes, remove the ice bath and stir overnight at room temperature. Dilute the reaction mixture with 200 mL dichloromethane, wash twice with 250 mL portions of 1 N NaHSO4, once with aqueous saturated sodium chloride, then dry over MgSO4 and concentrate to a brown solid. Purify on Biotage 75L® silica cartridge in 4.5:4.5:1 CH2Cl2:hexanes:diethyl ether to yield 4.33 g (48%) of the title compound as a pale yellow-ivory solid. LCMS (ES) m/z 381,383 (M−1).

Workup

  1. customto give a clear solution
  2. customRemove volatiles on rotovap to yield a clear yellow oil
  3. temperaturechill on ice
  4. stirringwith stirring over 30 minutes
  5. customremove the ice bath
  6. stirringstir overnight at room temperature
  7. additionDilute the reaction mixture with 200 mL dichloromethane
  8. washwash twice with 250 mL portions of 1 N NaHSO4, once with aqueous saturated sodium chloride
  9. dry with materialdry over MgSO4
  10. concentrationconcentrate to a brown solid
  11. customPurify on Biotage 75L® silica cartridge in 4.5:4.5:1 CH2Cl2

Sources & evidence

ORD record
ord-dfeb1dd5ade240d0a3394f6e9262dca0
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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