Triethylamine → trans-Ethyl 8-fluoro-3-phenyl-3a,4-dihydro-3h-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxylate

HRID 1867263Notes

Reaction equation

HRID 1867263 reaction equation
Cl/[C:2](=[N:8]/[NH:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[O:17][CH2:18]/[CH:19]=[CH:20]/[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)/[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(N(CC)CC)C.CCOC(C)=O>C1(C)C=CC=CC=1>[F:16][C:14]1[CH:13]=[CH:12][C:11]2[O:17][CH2:18][C@@H:19]3[C@H:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[N:8][N:9]3[C:10]=2[CH:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 89029529ethyl (2E)-2-chloro-2-[[5-fluoro-2-[(E)-3-phenylprop-2-enoxy]phenyl]hydrazinylidene]acetate

Product 1

HCID 91552591trans-Ethyl 8-fluoro-3-phenyl-3a,4-dihydro-3h-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Ethyl (2E)-chloro[(5-fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}phenyl)hydrazono]ethanoate (5-3, 3.1 g, 8.23 mmol) was dissolved in anhydrous toluene (20 mL) and treated with triethylamine (11.5 mL, 83 mmol). The reaction was heated at reflux for 24 h, and cooled. EtOAc (100 mL) was added and the organic layer was washed with 5% NaHCO3. The organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The crude was purified by flash column chromatography (120 g SiO2 Redisep, 0-30% EtOAc/hexanes gradient) to give pure trans-ethyl 8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxylate (5-4). 1H NMR (300 MHz, CDCl3) δ 7.32 (m, 6H), 6.86 (dd, J=8.9, 5.0 Hz, 1H), 6.68 (app dt, J=7.9, 3.1 Hz, 1H), 4.34-4.12 (m, 5H), 3.62 (t, J=10.7 Hz, 1H), 1.23 (t, J=7.0 Hz, 2H); MS (M+H+, C19H17FN2O3) 340.1 found 340.4 required.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. temperaturecooled
  4. washthe organic layer was washed with 5% NaHCO3
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by flash column chromatography (120 g SiO2 Redisep, 0-30% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-3fe9cd8ca1bd42ff8980c56b7fe74c63
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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