Sodium Bicarbonate → (5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanone

HRID 931547Notes

Reaction equation

HRID 931547 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([CH:8]([C:10]2[CH:15]=[C:14]([Cl:16])[N:13]=[C:12]([F:17])[C:11]=2[O:18][CH2:19][O:20][CH3:21])[OH:9])[CH:7]=1.C([O-])(O)=O.[Na+]>O.C(Cl)Cl.[K+].[Br-].CC1(C)N([O])C(C)(C)CCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([Cl:16])[N:13]=[C:12]([F:17])[C:11]=2[O:18][CH2:19][O:20][CH3:21])=[O:9])[CH:7]=1

Participants

7

Reactant 2

HCID 516892Sodium BicarbonateHCID 86658355(5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanol

Product 1

HCID 86658356(5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanoneYield 102.4%

Reagents, catalysts & solvents 4

HCID 253877Potassium BromideCatalystHCID 2724126TempoCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

A solution of KBr (65.1 g, 0.55 mol) in water (5.9 L) was added to a solution of (5-bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanol (2157 g, 5.47 mol) in DCM (5.9 L). The resulting biphasic mixture was cooled to 5° C. TEMPO (8.6 g, 0.055 mol) was added and the reaction mixture was stirred for 5 min. A solution of NaHCO3 (106 g, 1.26 mol, 0.23 eq) in bleach (6170 mL, 6.01 mol, 1.1 eq) was added slowly keeping the internal temperature below 10° C. After the addition was completed, the organic phase was separated. The aqueous layer was extracted with DCM (4 L×2). The combined organic layers were washed with 5% aqueous solution of sodium metabisulfite (6 L×1), brine (3 L×1) and dried over anhydrous Na2SO4. The solution was concentrated under reduced pressure to give 2200 g of (5-bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanone as a yellow solid.

Workup

  1. customthe internal temperature below 10° C
  2. additionAfter the addition
  3. customthe organic phase was separated
  4. extractionThe aqueous layer was extracted with DCM (4 L×2)
  5. washThe combined organic layers were washed with 5% aqueous solution of sodium metabisulfite (6 L×1), brine (3 L×1)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4abb9710f8134f76a7b946893c8ca3ac
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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