Iodine → Trifluoroacetic acid

HRID 69274Notes

Reaction equation

HRID 69274 reaction equation
II.[OH:3][PH2]=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([C:16]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[CH:27][CH:26]=[CH:25]4)([OH:21])[C:17]([F:20])([F:19])[F:18])=[CH:14][N:15]=2)[N:12]=1>C(O)(=O)C>[C:16]([OH:21])([C:17]([F:20])([F:19])[F:18])=[O:3].[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([CH:16]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[CH:27][CH:26]=[CH:25]4)[C:17]([F:18])([F:19])[F:20])=[CH:14][N:15]=2)[N:12]=1

Participants

6

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 866351161-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-2,2,2-trifluoro-1-(quinolin-6-yl)ethanol

Product 2

HCID 6422Trifluoroacetic acidHCID 57917412(Rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-2,2,2-trifluoro-ethyl]-quinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
150 °C

Procedure

Iodine (105 mg, 0.412 mmol) and H3PO2 (0.225 mL of a 50% aqueous solution, 2.059 mmol) were added to a solution of (rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-2,2,2-trifluoro-1-(quinolin-6-yl)ethanol (Stage 274.1, 52 mg, 0.137 mmol) in acetic acid (1.4 mL). The RM was heated at 150° C. for 45 min under microwave irradiations. The solvent was removed. The residue was taken up with EtOAc and extracted with 1N HCl twice. The combined aqueous layers was basified to pH 14 with NaOH pellets. It was then extracted with EtOAc/MeOH (9:1) twice. Combined organic layers was dried over Na2SO4, filtered and concentrated. After purification by preparative HPLC with acetonitrile and water (+0.1% TFA), the fraction containing the product was lyophilized to give a TFA salt of the title compound (tR 1.0 min (conditions 1), MH+=363).

Workup

  1. customThe solvent was removed
  2. extractionextracted with 1N HCl twice
  3. extractionIt was then extracted with EtOAc/MeOH (9:1) twice
  4. dry with materialCombined organic layers was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customAfter purification by preparative HPLC with acetonitrile and water (+0.1% TFA)
  8. additionthe fraction containing the product

Sources & evidence

ORD record
ord-16d5f39b9bf445a0ad74045b040cd1ae
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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