N-bromobutanimide → 5-Bromo-3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-2-pyridinamine

HRID 1845895Notes

Reaction equation

HRID 1845895 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@@H:10]([O:12][C:13]1[C:14]([NH2:19])=[N:15][CH:16]=[CH:17][CH:18]=1)[CH3:11].C1C(=O)N([Br:27])C(=O)C1.OS([O-])=O.[Na+]>ClCCl.C(#N)C>[Br:27][C:17]1[CH:18]=[C:13]([O:12][C@H:10]([C:3]2[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[Cl:1])[CH3:11])[C:14]([NH2:19])=[N:15][CH:16]=1

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 23665763Sodium BisulfiteHCID 86327671(S)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-aMine

Product 1

HCID 848193465-Bromo-3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-2-pyridinamineYield 83%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine (12 g, 39.87 mmol) was dissolved in dichloromethane (15 mL), a solution of N-bromosuccimide (7.1 g, 39.87 m mol) in acetonitrile (20 mL) was added dropwise slowly under the cooling of ice bath, and the reaction was stirred. After TLC test has showed that reaction was completed, a small amount of NaHSO3 solution was added to quench it, and the pH was adjusted to about 8-9 using sodium carbonate solution. The mixed solution was concentrated under reduced pressure to remove dichloromethane and acetonitrile. The residue was extracted with dichloromethane, and the organic layer was separated, washed with water, dried over anhydrous sodium sulfate, concentrated; the residue was purified via silica gel column chromatography (petroleum ether:ethyl acetate=4:1) to yield the target product as yellow solid (12.5 g, yield: 83%).

Workup

  1. temperaturecooling of ice bath
  2. customAfter TLC test has showed that reaction
  3. customto quench it
  4. concentrationThe mixed solution was concentrated under reduced pressure
  5. customto remove dichloromethane and acetonitrile
  6. extractionThe residue was extracted with dichloromethane
  7. customthe organic layer was separated
  8. washwashed with water
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customthe residue was purified via silica gel column chromatography (petroleum ether:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-837a37e6c6c14902970400bb5b71b443
Source dataset
uspto-grants-2015_02
Patent number
US08952002B2

Reaction notes

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