Acetic Acid → HCID 58307502, compound

HRID 222798Notes

Reaction equation

HRID 222798 reaction equation
[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[CH:20][C:19](=O)[O:18][C:17]=2[CH3:24])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1.C(O)C.O.[NH2:29][NH2:30].C(O)(=O)C.C([O-])([O-])=O.[Na+].[Na+]>>[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[CH:20][C:19](=[O:18])[N:29]([NH2:30])[C:17]=2[CH3:24])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 702EthanolHCID 10340Sodium CarbonateHCID 24654Hydrazine hydrate (1:1)2×HCID 58307469HCID 58307469, compound

Product 1

HCID 58307502HCID 58307502, compoundYield 33%

Conditions

Temperature
80 °C

Procedure

To a solution of 2,4-dimethyl-6-oxo-6H-pyran-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide (419 mg, 1.27 mmol) in ethanol (4.0 mL, 70 mmol) were added hydrazine hydrate (370 uL, 7.6 mmol) and acetic acid (4.0 mL, 70 mmol). The mixture was heated at 80° C. for 24 hrs. More hydrazine hydrate (371 uL, 7.63 mmol) was added and stirring continued for 7 hrs. The reaction mixture was adjusted to neutral pH by addition of aq. Sat. Na2CO3. The crude mixture was extracted with dichloromethane (4×40 mL), combined organic phases were washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash chromatography to give the title compound, yield 33%. LC-MS (m/z) 344.4 (MH+); tR=1.32 (method C). 1H NMR (600 MHz, CDCl3): 7.84 (d, J=8.6 Hz, 1H), 7.34 (td, J=7.9, 6.0 Hz, 1H), 7.20 (d, J=7.7 Hz, 1H), 7.17-7.11 (m, 1H), 6.99 (td, J=8.3, 2.0 Hz, 1H), 6.02 (s, 1H), 5.22 (s, 2H), 5.11-5.02 (m, 1H), 2.87-2.75 (m, 1H), 2.29 (s, 3H), 2.24 (m, 1H), 2.05 (s, 3H), 2.00-1.75 (m, 5H). 13C NMR (151 MHz, CDCl3) 166.34, 162.14, 159.96, 146.98, 143.64, 142.71, 130.10 (d, J=8.2 Hz, 1C), 122.78, 118.63, 114.34 (d, J=21.0 Hz, 1C), 114.14, 113.79 (d, J=21.6 Hz, 1C), 58.74, 40.05, 26.17, 25.59, 19.48, 17.49, 16.63.

Workup

  1. extractionThe crude mixture was extracted with dichloromethane (4×40 mL)
  2. washwere washed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a1f755aa84244b1cbc2d0c74a3931f5f
Source dataset
uspto-grants-2012_06
Patent number
US08207347B2

Reaction notes

Loading…