Hexamethylphosphoramide → HCID 178437721, compound

HRID 1458672Notes

Reaction equation

HRID 1458672 reaction equation
[F:1][C:2](I)([F:4])[F:3].CN(C)P(=O)(N(C)C)N(C)C.[C:17]([C@@H:21]1[CH2:26][CH2:25][C@H:24]([NH:27][C:28]2[C:33](I)=[C:32]([CH2:35][CH3:36])[N:31]=[CH:30][N:29]=2)[CH2:23][CH2:22]1)([CH3:20])([CH3:19])[CH3:18]>[Cu].C(OCC)C>[C:17]([C@@H:21]1[CH2:22][CH2:23][C@H:24]([NH:27][C:28]2[C:33]([C:2]([F:4])([F:3])[F:1])=[C:32]([CH2:35][CH3:36])[N:31]=[CH:30][N:29]=2)[CH2:25][CH2:26]1)([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 12679HexamethylphosphoramideHCID 16843TrifluoroiodomethaneHCID 178437728HCID 178437728, compound

Product 1

HCID 178437721HCID 178437721, compound

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

8.4 g of trifluoromethyl iodide and 5 g of copper powder were stirred with 20 ml of hexamethylphosphoric triamide in a stainless steel laboratory autoclave (Hastelloy) at 120° C. for 2.5 hours. The mixture was filtered with suction over Celite, under nitrogen, to remove the excess copper powder. 1.92 g (5 mmol) of 4-(cis-4-tert-butyl-cyclohexylamino)-6-ethyl-5-iodopyrimidine (Example 1) were added in order to dissolve the trifluoromethyl-copper complex, and the mixture was stirred under nitrogen at 100° C. for 2 hours. After cooling, 200 ml of diethyl ether were added, the precipitated copper salts were filtered off and the filtrate was extracted by stirring with water. The organic phase was dried and concentrated. The product was purified by filtration over a silica gel column (petroleum ether/ethyl acetate 7:3) to give 0.52 g (32% of theory) of product as a colorless oil.

Workup

  1. filtrationThe mixture was filtered with suction over Celite, under nitrogen
  2. customto remove the excess copper powder
  3. dissolutionto dissolve the trifluoromethyl-copper complex
  4. temperatureAfter cooling
  5. filtrationthe precipitated copper salts were filtered off
  6. extractionthe filtrate was extracted
  7. stirringby stirring with water
  8. customThe organic phase was dried
  9. concentrationconcentrated
  10. filtrationThe product was purified by filtration over a silica gel column (petroleum ether/ethyl acetate 7:3)
  11. customto give 0.52 g (32% of theory) of product as a colorless oil

Sources & evidence

ORD record
ord-253942af0fa34b9e9c4c7e915be29e0d
Source dataset
uspto-grants-1998_12
Patent number
US05852023

Reaction notes

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