N-Fluorobenzenesulfonimide → HCID 67406064, compound

HRID 625961Notes

Reaction equation

HRID 625961 reaction equation
[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([O:15][CH3:16])[C:10]([O:13][CH3:14])=[N:11][CH:12]=2)[CH:2]=1.[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:38])(=O)=O)=CC=1>C1COCC1.CCCCCC>[C:1]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[C:8]([F:38])=[C:9]([O:15][CH3:16])[C:10]([O:13][CH3:14])=[N:11][CH:12]=2)[CH:2]=1

Participants

6

Reactant 3

HCID 588007N-FluorobenzenesulfonimideHCID 67405602HCID 67405602, compoundHCID 178418339Butyllithium

Product 1

HCID 67406064HCID 67406064, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-(biphenyl-3-yl)-2,3-dimethoxypyridine (52 mg, 0.178 mmol) in THF (2 mL) at −78° C. was added n-BuLi solution in hexane (2.5 M, 0.157 mL) and then the −78° C. bath was replaced with a 0° C. cooling bath. After stirring at this temperature for 50 min, the reaction mixture was cooled down to −78° C. and then solid N-fluorobenzenesulfonimide was added to it. The reaction was quenched after 10 min by adding saturated aqueous NH4Cl solution and then partitioned between EtOAc and saturated aqueous NaHCO3 solution. Layers were separated and the aqueous solution was extracted with EtOAc (2×). Combined organic solutions were dried over Na2SO4 and concentrated. Purification by preparative HPLC (10-85% CH3CN/H2O over 20 min, 0.05% added TFA) afforded 16 mg (29%) of 5-(biphenyl-3-yl)-4-fluoro-2,3-dimethoxypyridine as a colorless viscous material. LC/MS (M+H)+ 310.2.

Workup

  1. customthe −78° C. bath
  2. customwas replaced with a 0° C.
  3. temperaturecooling bath
  4. customThe reaction was quenched after 10 min
  5. additionby adding saturated aqueous NH4Cl solution
  6. custompartitioned between EtOAc and saturated aqueous NaHCO3 solution
  7. customLayers were separated
  8. extractionthe aqueous solution was extracted with EtOAc (2×)
  9. dry with materialCombined organic solutions were dried over Na2SO4
  10. concentrationconcentrated
  11. customPurification
  12. additionby preparative HPLC (10-85% CH3CN/H2O over 20 min, 0.05% added TFA)

Sources & evidence

ORD record
ord-80e0774014a647d8bdb6d55f1f4c1903
Source dataset
uspto-grants-2016_04
Patent number
US09309199B2

Reaction notes

Loading…