Acetic Acid → HCID 11270256, compound

HRID 2118208Notes

Reaction equation

HRID 2118208 reaction equation
[C:1]([O:5][C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:22]2[CH:27]=[CH:26][C:25](C=O)=[CH:24][CH:23]=2)=[C:13](\[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)/[CH2:14][CH3:15])=[CH:8][CH:7]=1)(=[O:4])[CH2:2][CH3:3].[C:30]([OH:36])(=[O:35])[CH2:31][C:32](O)=O.N1C=CC=CC=1.C(O)(=O)C>CC#N.O.CCCCCCC.N1CCOCC1>[C:16]1(/[C:13](/[CH2:14][CH3:15])=[C:12](/[C:22]2[CH:27]=[CH:26][C:25](/[CH:32]=[CH:31]/[C:30]([OH:36])=[O:35])=[CH:24][CH:23]=2)\[C:9]2[CH:10]=[CH:11][C:6]([O:5][C:1](=[O:4])[CH2:2][CH3:3])=[CH:7][CH:8]=2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 867Malonic AcidHCID 1049PyridineHCID 86760739HCID 86760739, compound

Product 1

HCID 11270256HCID 11270256, compoundYield 80.3%

Reagents, catalysts & solvents 4

HCID 8083MorpholineCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent3×HCID 8900HeptaneSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of 11 (20.0 g, 52 mmol) and malonic acid (8.10 g, 100 mmol) was added, sequentially, CH3CN (100 mL), pyridine (2.1 mL, 30 mmol) and morpholine (0.09 mL, 1.0 mmol). The mixture was then heated to reflux and the solvent distilled. The volume of the reaction was maintained constant by addition of fresh CH3CN until ˜30 volumes of solvent were distilled. The reaction was then cooled to 5° C. and a solution of acetic acid (2.08 mL, 36 mmol) in CH3CN (20 mL) added. The precipitated solid was filtered, washed with cold CH3CN (40 mmol) and H2O (40 mL) then slurried overnight in heptane (150 mL) at 35° C. The solid was filtered, rinsed with heptane (40 mL) and dried overnight in vacuo to yield 17.8 g (80%) of the title compound 7 as a white solid. 1HNMR (DMSO-d6): δ 0.26 (s, 6H), 0.83 (t, J=7.5 Hz, 3H), 0.94 (s, 9H), 2.35 (q, J=7.5 Hz, 2H), 6.39 (d, J=8.4 Hz, 2H), 6.53 (d, J=16 Hz, 1H), 6.58 (d, J=8.4 Hz, 2H), 7.06-7.18 (m, 5H), 7.2 (d, J=8 Hz, 2H), 7.59 (d, J=16 Hz, 1H), 7.69 (d, J=8 Hz, 2H), 9.19 (s, 1H); MS, m/z 485 (M+H)+.

Workup

  1. additionwas added
  2. temperatureThe mixture was then heated
  3. temperatureto reflux
  4. distillationthe solvent distilled
  5. temperatureThe volume of the reaction was maintained constant by addition of fresh CH3CN until ˜30 volumes of solvent
  6. distillationwere distilled
  7. filtrationThe precipitated solid was filtered
  8. filtrationThe solid was filtered
  9. washrinsed with heptane (40 mL)
  10. customdried overnight in vacuo

Sources & evidence

ORD record
ord-5fbe675134a84e528a844d1c585e3d74
Source dataset
uspto-grants-2008_10
Patent number
US07442833B2

Reaction notes

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