Triethylamine → 2-(2-(4-Hydroxycyclohexyl)aminoanilin-5-yl)benzoxazole

HRID 74219Notes

Reaction equation

HRID 74219 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][C:3]=1[N+:17]([O-])=O.C(N(CC)CC)C.Cl.[NH2:28][CH:29]1[CH2:34][CH2:33][CH:32]([OH:35])[CH2:31][CH2:30]1.[H][H]>[C].[Pd].CO.O1CCCC1.C(#N)C>[OH:35][CH:32]1[CH2:33][CH2:34][CH:29]([NH:28][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:9][C:10]4[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=4[N:12]=3)=[CH:4][C:3]=2[NH2:17])[CH2:30][CH2:31]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 522619(1s,4s)-4-Aminocyclohexan-1-ol hydrochlorideHCID 219909702-(4-Fluoro-3-nitrophenyl)benzoxazoleHCID 178418361HCID 178418361, compound

Product 1

HCID 680856372-(2-(4-Hydroxycyclohexyl)aminoanilin-5-yl)benzoxazoleYield 67.2%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 6342AcetonitrileSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

2-(4-Fluoro-3-nitrophenyl)benzoxazole (see Working Example 15-2) (0.60 g, 2.3 mmol) was added to an acetonitrile (20 mL) solution containing triethylamine (0.70 g, 7.0 mmol) and 4-aminocyclohexanol hydrochloride (0.53 g, 2.5 mmol), and this was heated to reflux for 2 hours with stirring. After the reaction was complete, this was cooled to room temperature, and the crystals precipitated by the addition of water were filtered. After the crystals were washed with water, they were dried under reduced pressure with heating to give crystals that were added to a solution of a solvent mixture of methanol/tetrahydrofuran (1:1, 20 mL) including 10% palladium-carbon (50 mg). A hydrogen atmosphere was substituted in the flask, and this was stirred at room temperature for 8 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (0.50 g, 67% yield) as pale red crystals.

Workup

  1. temperaturethis was heated
  2. temperatureto reflux for 2 hours
  3. customthe crystals precipitated by the addition of water
  4. filtrationwere filtered
  5. washAfter the crystals were washed with water, they
  6. customwere dried under reduced pressure
  7. temperaturewith heating
  8. customto give crystals that
  9. stirringthis was stirred at room temperature for 8 hours
  10. filtrationthis was filtered through Celite
  11. concentrationthe filtrate was concentrated
  12. customThe residue obtained
  13. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b2aee45478de454da67e5904b66ba0eb
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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