Sodium hydride → HCID 59556581, compound

HRID 1172976Notes

Reaction equation

HRID 1172976 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[H][H].[Cl:11][C:12]1[CH:13]=[C:14]([C:22]2[N:26]=[C:25]([C:27]3[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]\[C:35]([O:37][CH3:38])=[O:36])=[CH:29][CH:28]=3)[O:24][N:23]=2)[CH:15]=[CH:16][C:17]=1[O:18][CH:19]([CH3:21])[CH3:20]>CS(C)=O.[Cl-].[Na+].O>[Cl:11][C:12]1[CH:13]=[C:14]([C:22]2[N:26]=[C:25]([C:27]3[CH:28]=[CH:29][C:30]([C@@H:33]4[CH2:2][C@H:34]4[C:35]([O:37][CH3:38])=[O:36])=[CH:31][CH:32]=3)[O:24][N:23]=2)[CH:15]=[CH:16][C:17]=1[O:18][CH:19]([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 59556579HCID 59556579, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59556581HCID 59556581, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 5234Sodium ChlorideSolvent

Procedure

To a stirred suspension of trimethylsulfoxonium iodide (234 mg, 1.065 mmol) in DMSO (5.0 mL) under nitrogen, was added, in portions NaH (42.6 mg, 1.065 mmol), with a water bath in place to keep the reaction between 25-30° C. Upon completion of hydrogen evolution, a solution of (Z)-methyl 3-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)acrylate (386 mg, 0.968 mmol) in DMSO (5.00 mL) was added drop-wise, keeping the reaction temperature at or below 35° C. After addition was complete, the reaction was stirred at room temperature for an hour and a half and then warmed to 50° C. for two hours. 50 ml of water was then added to the reaction, and the reaction left to stir at room temperature overnight. The reaction mixture was diluted with saturated aqueous sodium chloride, and the aqueous layer was extracted 3× with 75 mL EtOAc. Organic layers were combined, dried over MgSO4, and concentrated. The crude material was purified by RP-HPLC (A=50 mM ammonium acetate, B=ACN; 30% to 100% B over 30 min at 21.0 mL/min; UV λ=254 nm; Thermo Hyperprep HS C18, 8 μm, 250×21.2 mm column). Fractions containing product were combined, concentrated and lyophilized to give Trans-methyl 2-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)cyclopropanecarboxylate (155 mg, 39%) as a white solid. LCMS (Table 1, Method c) Rt=3.27 min, m/z 413.17 (M+H)+. 1H NMR (400 MHz, DMSO) δ ppm 8.08 (d, 2H), 8.06 (d, 1H), 7.99 (dd, 1H), 7.47 (d, 2H), 7.39 (d, 1H), 4.82 (sept, 1H), 3.66 (s, 3H), 2.59 (ddd, 1H), 2.12 (ddd, 1H), 1.58 (ddd, 1H), 1.53 (ddd, 1H), 1.35 (d, 6H).

Workup

  1. customthe reaction between 25-30° C
  2. custombelow 35° C
  3. additionAfter addition
  4. temperaturea half and then warmed to 50° C. for two hours
  5. waitthe reaction left
  6. stirringto stir at room temperature overnight
  7. extractionthe aqueous layer was extracted 3× with 75 mL EtOAc
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude material was purified by RP-HPLC (A=50 mM ammonium acetate, B=ACN
  11. additionFractions containing product
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-ce5505a394284ef2b788c84ed2cc111c
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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