Diisopropylethylamine → 2-(4-(Cyclopropylmethoxy)-3-fluorophenyl)-1,3-benzoxazol-6-ol

HRID 2277132Notes

Reaction equation

HRID 2277132 reaction equation
Cl.[NH2:2][C:3]1[CH:9]=[CH:8][C:6]([OH:7])=[CH:5][C:4]=1[OH:10].[CH:11]1([CH2:14][O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=O)=[CH:18][C:17]=2[F:25])[CH2:13][CH2:12]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH:11]1([CH2:14][O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]3[O:10][C:4]4[CH:5]=[C:6]([OH:7])[CH:8]=[CH:9][C:3]=4[N:2]=3)=[CH:18][C:17]=2[F:25])[CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 134088224-Aminobenzene-1,3-diol hydrochlorideHCID 286047044-(Cyclopropylmethoxy)-3-fluorobenzoic acid

Product 1

HCID 867311872-(4-(Cyclopropylmethoxy)-3-fluorophenyl)-1,3-benzoxazol-6-olYield 26.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-aminoresorcinol hydrochloride (5.00 g), 4-(cyclopropylmethoxy)-3-fluorobenzoic acid (5.91 g) and diisopropylethylamine (7.37 mL) in DMF (50 mL) was added HATU (11.8 g), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained solid was washed with ethyl acetate. To a solution of the obtained solid, hexachloroethane (16.7 g) and triphenylphosphine (18.5 g) in acetonitrile (50 mL) was added triethylamine (11.8 mL), and the mixture was stirred at room temperature for 15 min, and then with heating at 80° C. for 2 hr. The reaction mixture was filtered, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (2.23 g).

Workup

  1. washwashed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. washthe obtained solid was washed with ethyl acetate
  5. additionTo a solution of the obtained solid, hexachloroethane (16.7 g) and triphenylphosphine (18.5 g) in acetonitrile (50 mL) was added triethylamine (11.8 mL)
  6. stirringthe mixture was stirred at room temperature for 15 min
  7. temperaturewith heating at 80° C. for 2 hr
  8. filtrationThe reaction mixture was filtered
  9. customthe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-5d5ee0b1e0f6462991cabfedcf847fbe
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

Loading…