Pyridine → HCID 18387406, compound

HRID 2296694Notes

Reaction equation

HRID 2296694 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:17])([CH2:13][CH2:14][CH2:15][CH3:16])[C:9]([F:12])([F:11])[F:10])=[CH:6][C:5]([Cl:18])=[CH:4][CH:3]=1.N1C=CC=CC=1.Br[CH2:26][C:27](Br)=[O:28]>CCOCC>[CH2:13]([C:8]1([C:9]([F:10])([F:11])[F:12])[C:7]2[CH:6]=[C:5]([Cl:18])[CH:4]=[CH:3][C:2]=2[NH:1][C:27](=[O:28])[CH2:26][O:17]1)[CH2:14][CH2:15][CH3:16]

Participants

5

Reactant 3

HCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 54071254HCID 54071254, compound

Product 1

HCID 18387406HCID 18387406, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred ice-cooled solution of 185 mg of 6-amino-3-chloro-α-butyl-α-(trifluoromethyl)benzyl alcohol in 15 ML of dry ether was added 0.100 mL of dry pyridine and 0.060 mL 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 8 mL of dry DMF and was treated at room temperature with 40 mg of 100% sodium hydride for 16 h. The reaction was partitioned between ethyl acetate and water and the ethyl acetate layer was washed with brine, dried, and evaporated. The crude product was purified first by column chromatography over silica gel (elution with ethyl acetate/hexanes 1:3), and then by preparative silica gel TLC (elution with 2.5% methanol in methylene chloride) affording 32 mg of the title compound as an amorphous solid: HRMS: Calcd. for C14H16NO2ClF3 (M+H)+: 322.082166. Found: 322.080685.

Workup

  1. washwashed with water and aqueous sodium bicarbonate
  2. customdried
  3. customevaporated
  4. dissolutionThe residue was dissolved in 8 mL of dry DMF
  5. additionwas treated at room temperature with 40 mg of 100% sodium hydride for 16 h
  6. customThe reaction was partitioned between ethyl acetate and water
  7. washthe ethyl acetate layer was washed with brine
  8. customdried
  9. customevaporated
  10. customThe crude product was purified first by column chromatography over silica gel (elution with ethyl acetate/hexanes 1:3)
  11. washby preparative silica gel TLC (elution with 2.5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-45fd715ed653496d9cc15790456c1f64
Source dataset
uspto-grants-2002_12
Patent number
US06489320B1

Reaction notes

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