Triphenylphosphine → 3-methyl-2-[2-methyl-4-(4-piperidinyloxy)phenyl]-4(3H)-quinazolinone

HRID 2422651Notes

Reaction equation

HRID 2422651 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]([CH3:18])[C:16](=[O:19])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)=[C:4]([CH3:20])[CH:3]=1.O[CH:22]1[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(OCC)(=O)C.O>[CH3:18][N:17]1[C:16](=[O:19])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([O:1][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:3][C:4]=1[CH3:20]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 136343912HCID 136343912, compound

Product 1

HCID 672457473-methyl-2-[2-methyl-4-(4-piperidinyloxy)phenyl]-4(3H)-quinazolinoneYield 93.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-(4-Hydroxy-2-methylphenyl)-3-methyl-4(3H)-quinazolinone (200 mg, 0.751 mmol), tert-butyl 4-hydroxytetrahydro-1(2H)-pyridinecarboxylate (227 mg, 1.12 mmol) and triphenyl phosphine (295 mg, 1.12 mmol) were dissolved in THF (2.0 mL), and with stirring at 0° C., diisopropyl azodicarboxylate (228 mg, 1.12 mmol) was added thereto and stirred for 24 hours. The reaction solution was diluted with ethyl acetate, poured into saturated saline water, extracted with ethyl acetate, and the organic layer was dried with magnesium sulfate. The solvent was evaporated off, and the resulting residue was dissolved in chloroform (3 mL), trifluoroacetic acid (2 mL) was added thereto, and stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate, washed with aqueous 1 N sodium hydroxide solution and saturated saline water, and the organic layer was dried with magnesium sulfate. The solvent was evaporated off, and the residue was purified through silica gel column chromatography (chloroform/methanol=1/1) to obtain the intended compound (245 mg, 93%) as a colorless solid.

Workup

  1. stirringstirred for 24 hours
  2. extractionextracted with ethyl acetate
  3. dry with materialthe organic layer was dried with magnesium sulfate
  4. customThe solvent was evaporated off
  5. dissolutionthe resulting residue was dissolved in chloroform (3 mL)
  6. additiontrifluoroacetic acid (2 mL) was added
  7. stirringstirred at room temperature for 2 hours
  8. additionThe reaction solution was diluted with ethyl acetate
  9. washwashed with aqueous 1 N sodium hydroxide solution and saturated saline water
  10. dry with materialthe organic layer was dried with magnesium sulfate
  11. customThe solvent was evaporated off
  12. customthe residue was purified through silica gel column chromatography (chloroform/methanol=1/1)

Sources & evidence

ORD record
ord-b7586e116c0c4f349986e98c0e4b637f
Source dataset
uspto-grants-2011_06
Patent number
US07960394B2

Reaction notes

Loading…