Trifluoroacetic acid → 4-Chloro-5-(2-isopropyl-4,5-dimethoxy-benzyl)-2-methylsulfanyl-pyrimidine

HRID 81746Notes

Reaction equation

HRID 81746 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([C:10]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[CH:12][C:11]=2[CH:20]([CH3:22])[CH3:21])O)=[CH:6][N:5]=[C:4]([S:23][CH3:24])[N:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:7]([CH2:8][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[CH:12][C:11]=2[CH:20]([CH3:21])[CH3:22])=[CH:6][N:5]=[C:4]([S:23][CH3:24])[N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 59598617(4-Chloro-2-methylsulfanyl-pyrimidin-5-yl)-(2-isopropyl-4,5-dimethoxy-phenyl)-methanol

Product 1

HCID 595986204-Chloro-5-(2-isopropyl-4,5-dimethoxy-benzyl)-2-methylsulfanyl-pyrimidineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-chloro-2-methylsulfanyl-pyrimidin-5-yl)-(2-isopropyl-4,5-dimethoxy-phenyl)-methanol (6.5 g, 17.6 mmol) in 200 mL CH2Cl2 was added triethylsilane (28.0 mL, 176 mmol) and trifluoroacetic acid (TFA) (70 mL, 881 mmol). After 2 hours the solution was concentrated in vacuo, 10% K2CO3 was added and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (4:1 hexanes/ethyl acetate) afforded 4-chloro-5-(2-isopropyl-4,5-dimethoxy-benzyl)-2-methylsulfanyl-pyrimidine (5.60 g, 91%) as a clear oil.

Workup

  1. concentrationAfter 2 hours the solution was concentrated in vacuo, 10% K2CO3
  2. additionwas added
  3. extractionextracted with CH2Cl2
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification via flash chromatography (4:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-9710bc68e04344ccb7de892b316fe5bf
Source dataset
uspto-grants-2014_09
Patent number
US08846705B2

Reaction notes

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