Ammonium Chloride → HCID 86638494, compound

HRID 216341

Reaction equation

HRID 216341 reaction equation
Br[C:2]([P:5](=[O:10])([O-:9])[O:6][CH2:7][CH3:8])([F:4])[F:3].[CH:11]([Mg]Cl)(C)[CH3:12].[F:16][C:17]1[C:24]([F:25])=[C:23]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][N:27]=2)[CH:22]=[CH:21][C:18]=1[CH:19]=[O:20].[Cl-].[NH4+]>O1CCCC1.CC(C)=O.C(Cl)Cl>[F:16][C:17]1[C:24]([F:25])=[C:23]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][N:27]=2)[CH:22]=[CH:21][C:18]=1[CH:19]([OH:20])[C:2]([P:5](=[O:10])([O:9][CH2:11][CH3:12])[O:6][CH2:7][CH3:8])([F:4])[F:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 86638495HCID 86638495, compoundHCID 866384972,3-Difluoro-4-(5-fluoropyridin-2-yl)benzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 86638494HCID 86638494, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Conditions

Temperature
-78 °C

Procedure

A solution of ethyl bromodifluoromethylphosphonate (3.2 g, 12.1 mmol) in tetrahydrofuran (20 mL) was added dropwise to a solution of isopropylmagnesium chloride (2 M in tetrahydrofuran) (6.1 mL, 12.1 mmol) in tetrahydrofuran (20 mL) at −78° C. After stirring at −78° C. for 5 min, a solution of 2,3-difluoro-4-(5-fluoropyridin-2-yl)benzaldehyde (1.92 g, 8.1 mmol) in tetrahydrofuran (20 mL) was added dropwise. After stirring for a further 5 min at −78° C. then a further 1 h between −78 and 0 then a further 1 h between 0 and ambient temperature. The reaction mixture was poured into saturated ammonium chloride and extracted with methylene chloride. Combined extracts were washed with saturated aqueous sodium bicarbonate, dried (sodium sulfate) and concentrated in vacuo to afford a slightly yellow oil. Chromatography over silica eluting with 0-40% acetone/methylene chloride afforded diethyl {2-[2,3-difluoro-4-(5-fluoropyridin-2-yl)phenyl]-1,1-difluoro-2-hydroxyethyl}phosphonate as an off-white solid.

Workup

  1. stirringAfter stirring for a further 5 min at −78° C.
  2. customa further 1 h
  3. customa further 1 h between 0 and ambient temperature
  4. extractionextracted with methylene chloride
  5. washCombined extracts were washed with saturated aqueous sodium bicarbonate
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customto afford a slightly yellow oil

Sources & evidence

ORD record
ord-0c6c457868c742259cdaa7875a2be4f2
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Linked notes

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