Pyridine → HCID 5327773, compound

HRID 2296685Notes

Reaction equation

HRID 2296685 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:18])([C:13]#[C:14][CH:15]([CH3:17])[CH3:16])[C:9]([F:12])([F:11])[F:10])=[CH:6][C:5]([Cl:19])=[CH:4][CH:3]=1.N1C=CC=CC=1.Br[CH2:27][C:28](Br)=[O:29].[H-].[Na+]>CCOCC>[Cl:19][C:5]1[CH:4]=[CH:3][C:2]2[NH:1][C:28](=[O:29])[CH2:27][O:18][C:8]([C:13]#[C:14][CH:15]([CH3:16])[CH3:17])([C:9]([F:10])([F:11])[F:12])[C:7]=2[CH:6]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 24758Sodium hydrideHCID 61147Bromoacetyl bromideHCID 54340287HCID 54340287, compound

Product 1

HCID 5327773HCID 5327773, compoundYield 62.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred ice-cooled solution of 4.37 g (15 mmol) of 6-amino-3-chloro-α-(isopropylethynyl)-α-(trifluoromethyl)benzyl alcohol in 200 mL of dry ether was added 2.4 mL of dry pyridine and, quickly dropwise, 1.40 mL (16 mmol) of bromoacetyl bromide. After 30 min, the reaction mixture was diluted with ether, washed with water and aqueous sodium bicarbonate, dried and evaporated. The residue was dissolved in 150 mL of dry DMF and was treated at 0° with 400 mg of 100% sodium hydride (16.7 mmol) for 20 min. The cooling bath was removed, and the reaction was allowed to proceed at ambient temperature for 1.5 h. The reaction mixture was poured onto a mixture of 1.2 L of water and 300 mL of saturated aqueous sodium chloride and this was extracted 3 times with ether. The combined extracts were washed with brine, dried, and evaporated to a solid which was crystallized by dissolving in hot ethyl acetate and adding hexanes. This material was recrystallized from ethyl acetate/hexane to afford 3.125 g of pure title compound as a crystalline solid: mp 183-183.5°; HRMS Calcd. for C15H14NO2ClF3 (M+H)+: 332.066516. Found: 332.065892.

Workup

  1. washwashed with water and aqueous sodium bicarbonate
  2. customdried
  3. customevaporated
  4. dissolutionThe residue was dissolved in 150 mL of dry DMF
  5. customThe cooling bath was removed
  6. waitto proceed at ambient temperature for 1.5 h
  7. additionThe reaction mixture was poured onto a mixture of 1.2 L of water and 300 mL of saturated aqueous sodium chloride
  8. extractionthis was extracted 3 times with ether
  9. washThe combined extracts were washed with brine
  10. customdried
  11. customevaporated to a solid which
  12. customwas crystallized
  13. dissolutionby dissolving in hot ethyl acetate
  14. additionadding hexanes
  15. customThis material was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-8746e220bd7c484aa47c22aaa3ec1949
Source dataset
uspto-grants-2002_12
Patent number
US06489320B1

Reaction notes

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