Water → 6-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

HRID 407606Notes

Reaction equation

HRID 407606 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[C:12]([F:14])[CH:13]=1)[C:10](=O)[O:9][CH:8]2OC)([CH3:4])([CH3:3])[CH3:2].O.[NH2:19][NH2:20].O>C(O)(=O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[C:12]([F:14])[CH:13]=1)[C:10](=[O:9])[NH:20][N:19]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 866839105-(tert-Butyl)-7-fluoro-3-methoxyisobenzofuran-1(3H)-one

Product 1

HCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-oneYield 37.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 101g (40 g, 168 mmol) in glacial acetic acid (360 mL) was added hydrazine monohydrate (240 mL) at 0-10° C. under N2 protection. The resulting slurry was stirred under nitrogen at 50° C. for 1.5 hours. The reaction mixture was poured into 300 mL of water with continuous stirring. The aqueous phase was extracted with DCM (2×500 mL), and the combined organic phase was dried over Na2SO4, filtered and concentrated to give a residue, which was purified by re-crystallization in DMC and Et2O to provide 101h (17 g, 37.6% over 2 steps) as an off-white solid. 1HNMR (300 MHz, CDCl3) δ 8.11 (d, J=2.7 Hz, 1H), 7.46 (m, 2H), 1.39 (s, 9H). LCMS (ESI) m/z 221 (M+H)+.

Workup

  1. extractionThe aqueous phase was extracted with DCM (2×500 mL)
  2. dry with materialthe combined organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue, which
  6. customwas purified by re-crystallization in DMC and Et2O

Sources & evidence

ORD record
ord-c70fa77071ae430ca024f1638a8eb7c6
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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