Iodine → HCID 23512791, compound

HRID 2304910Notes

Reaction equation

HRID 2304910 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][CH:8]=[CH:9][CH:10]=1)=O.[BH4-].[Na+].II.CO>C1COCC1>[CH3:1][NH:2][CH2:3][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 807IodineHCID 887MethanolHCID 4311764Sodium borohydrideHCID 22962031HCID 22962031, compound

Product 1

HCID 23512791HCID 23512791, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

At 0° C. a solution of 4′-(trifluoromethyl)biphenyl-2-carboxylic acid methylamide (8.50 g, 36.44 mmol) in THF (100 ml) was added to a suspension of sodium borohydride (2.8 g, 73.05 mmol) in THF (50 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of iodine (7.70 g, 36.44 mmol) in THF (100 ml) was added dropwise. The reaction mixture was heated to reflux for 16 hours. It was cooled to 0° C. Methanol (200 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in tert-butyl methyl ether (150 ml) and a 20% aqueous solution of sodium hydroxide (150 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×80 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g) using DCM/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 2.35 g of N-methyl-N-((4′-(trifluoromethyl)biphenyl-2-yl)methyl)amine.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 16 hours
  3. temperatureIt was cooled to 0° C
  4. customThe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in tert-butyl methyl ether (150 ml)
  6. customThe phases were separated
  7. extractionThe aqueous phase was extracted with tert-butyl methyl ether (2×80 ml)
  8. dry with materialThe combined organic layers were dried over magnesium sulphate
  9. customThe solvent was removed in vacuo
  10. customThe crude product was purified by flash chromatography on silica (400 g)

Sources & evidence

ORD record
ord-03b9010bec3e4258aeb82d67e73909c9
Source dataset
uspto-grants-2002_08
Patent number
US06437147B1

Reaction notes

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