Water → HCID 66933278, compound

HRID 1364171Notes

Reaction equation

HRID 1364171 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:17]#[CH:18])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@H:12]([CH:14]1[CH2:16][CH2:15]1)[CH3:13])[CH2:7]2.C(=O)([O-])O.[K+].O.Cl[C:26](=[N:32][OH:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:17]2[O:33][N:32]=[C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:18]=2)[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@H:12]([CH:14]1[CH2:16][CH2:15]1)[CH3:13])[CH2:7]2

Participants

6

Reactant 4

HCID 962WaterHCID 516893Potassium BicarbonateHCID 6816376Ethyl chloro(hydroximino)acetate3×HCID 86636879HCID 86636879, compound

Product 1

HCID 66933278HCID 66933278, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

7-chloro-2-((S)-1-cyclopropylethyl)-5-ethynylisoindolin-1-one (28.66 g, 110.35 mmol) and potassium hydrogen carbonate (110.0 g, 1103.45 mmol) were dissolved in a solution consisting of 1200 mL of ethyl acetate and 400 mL of water. To this solution was added ethyl 2-chloro-2-(hydroxyimino)acetate (66.9 g, 441.38 mmol). The ethyl 2-chloro-2-(hydroxyimino)acetate was added at room temperature as a solution in 160 mL of ethyl acetate via syringe pump at a rate of 5 mL/Hr. Following the addition of the ethyl 2-chloro-2 (hydroxyimino)acetate, the reaction was allowed to continue stirring at room temperature for an additional 12 hours. The ethyl acetate layer was extracted in a separatory funnel, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on silica gel eluting with a gradient of 0 to 25% ethyl acetate in hexane to afford the title compound as a white solid (17.05 g, 41.2%). 1H NMR (300 MHz, CDCl3) δ ppm 0.36-0.53 (m, 3H) 0.63-0.73 (m, 1H) 0.98-1.12 (m, 1H) 1.38 (d, 3H) 1.47 (t, 3H) 3.80 (dq, 1H) 4.43-4.65 (m, 4H) 7.05 (s, 1H) 7.83 (s, 2H). MS ESI, m/z=375 (M+H). HPLC Method B: 0.82 min

Workup

  1. extractionThe ethyl acetate layer was extracted in a separatory funnel
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe material was purified by flash chromatography on silica gel eluting with a gradient of 0 to 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-be142d522305490682bcbcf7567124ba
Source dataset
uspto-grants-2011_02
Patent number
US07888353B2

Reaction notes

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