Potassium Phosphate, Tribasic → 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]pyrimidine

HRID 1024836Notes

Reaction equation

HRID 1024836 reaction equation
C12BC(CCC1)CCC2.[CH3:10][C:11]1([CH3:18])[O:16][CH2:15][C:14](=[CH2:17])[CH2:13][O:12]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[Cl:52][C:53]1[CH:58]=[C:57](Cl)[N:56]=[C:55]([S:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:63]=2[F:69])[N:54]=1>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:52][C:53]1[CH:58]=[C:57]([CH2:17][CH:14]2[CH2:15][O:16][C:11]([CH3:18])([CH3:10])[O:12][CH2:13]2)[N:56]=[C:55]([S:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:63]=2[F:69])[N:54]=1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 139114312,2-Dimethyl-5-methylidene-1,3-dioxaneHCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

Product 1

HCID 866198634-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]pyrimidine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 0.5M 9-borabicyclo[3.3.1]nonane (9-BBN) in tetrahydrofuran (17.12 ml) and 2,2-dimethyl-5-methylene-1,3-dioxane (Tet. Lett. (1988) 29 (45) 5703-5706) (1.3 g) was heated at 45° C. for 18 h. The solution was cooled and added to mixture of palladium(II)acetate, potassium phosphate (1.16 g), (biphenyl-2-yl)dicyclohexyl-phosphine (0.14 g) and 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (1.5 g) stirred under nitrogen. The mixture was heated in a microwave at 70° C., 250 W for a total of 1.5 h, then 70° C. on a hot-plate for 2 days. The reaction mixture was adsorbed onto silica-gel, the solvent evaporated under reduced pressure and the residue purified by flash silica-gel chromatography eluting with 20% ethyl acetate in iso-hexane to give a yellow oil. The oil was further purified by flash silica-gel chromatography eluting with dichloromethane to give the sub-title product as a viscous oil. Yield: 110 mg.

Workup

  1. temperatureThe solution was cooled
  2. customthe solvent evaporated under reduced pressure
  3. customthe residue purified by flash silica-gel chromatography
  4. washeluting with 20% ethyl acetate in iso-hexane
  5. customto give a yellow oil
  6. customThe oil was further purified by flash silica-gel chromatography
  7. washeluting with dichloromethane

Sources & evidence

ORD record
ord-9084462468f749538ee7cdb6e213afef
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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