Acetic Acid → HCID 56654741, compound

HRID 1961547Notes

Reaction equation

HRID 1961547 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:26]1([C:35]#[N:36])[CH2:29][N:28]([C:30]([CH:32]2[CH2:34][CH2:33]2)=[O:31])[CH2:27]1.C(O)(=O)C>C1COCC1.[Zn]>[CH:32]1([C:30]([N:28]2[CH2:29][C:26]([C:3]3[CH:2]=[CH:7][C:6]([C:8]4[CH2:12][C:11]([C:17]5[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=5)([C:13]([F:15])([F:14])[F:16])[O:10][N:9]=4)=[CH:5][CH:4]=3)([C:35]#[N:36])[CH2:27]2)=[O:31])[CH2:34][CH2:33]1

Participants

6

Reactant 2

HCID 176Acetic Acid2×HCID 56654400HCID 56654400, compound

Product 1

HCID 56654741HCID 56654741, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranCatalystHCID 23994ZincCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

The compound of Example 86 (60 mg) was dissolved in THF (2 mL) and Rieke Zn in THF was then added dropwise (2 mL of a 0.7N solution). The mixture was then sonicated for 5 minutes. LC-MS (THF+a few drops of acetic acid) shows about 50% conversion. Another 4 equivalents of Zn was added, and again 15 minutes sonication. LC-MS shows the reaction mixture is gone to about 90% conversion. About 200 μL of acetic acid was then added, the reaction mixture was stirred for 2 minutes, then filtered over celite. The solution was concentrated under vacuum and the remaining oil dissolved in ethyl acetate and washed with NaHCO3, then dried over MgSO4, filtered and concentrated in vacuum. The remaining oil is purified via reverse phase chromatography. Yield 55 mg. LC-MS confirms desired product [m/z 542]. NMR 400 MHz δ ppm: 7.78 (d, 2H), 7.67 (d, 2H), 7.66 (s, 2H), 4.99 (m, 1H), 4.71 (m, 1H), 4.53 (m, 1H), 4.39 (m, 1H), 4.10 (d, 1H), 3.71 (d, 1H), 1.45-1.39 (m, 1H), 1.10-1.06 (m, 2H), 0.91-0.86 (m, 2H).

Workup

  1. customThe mixture was then sonicated for 5 minutes
  2. customagain 15 minutes sonication
  3. filtrationfiltered over celite
  4. concentrationThe solution was concentrated under vacuum
  5. dissolutionthe remaining oil dissolved in ethyl acetate
  6. washwashed with NaHCO3
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuum
  10. customThe remaining oil is purified via reverse phase chromatography

Sources & evidence

ORD record
ord-c521af12043043649dc343da71a60e5a
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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