Sulfoxonium, trimethyl-, iodide (1:1) → HCID 71602481, compound

HRID 1411104Notes

Reaction equation

HRID 1411104 reaction equation
[I-].C[S+](C)(C)=O.[CH3:7]C([O-])(C)C.[K+].[CH2:13]=[C:14]1[C:27](=[O:28])[N:17]2[C@@H:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:19][CH2:20][C@@H:16]2[CH2:15]1>C1COCC1>[C:21]1([C@@H:18]2[N:17]3[C:27](=[O:28])[C:14]4([CH2:7][CH2:13]4)[CH2:15][C@H:16]3[CH2:20][O:19]2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 59493353HCID 59493353, compound

Product 1

HCID 71602481HCID 71602481, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Trimethylsulfoxonium iodide [Me3S(O)I] (1.5 eq) and anhydrous THF (12 vol) were charged to a reactor. Cooled to 10˜20° C. and then added t-BuOK (1.5 eq). The resulting mixture was warmed to 60±5° C. and stirred for 1 h. Cooled down back to 10˜20° C. and then dropwise added a solution of (3R,7aS)-6-methylene-3-phenyltetrahydropyrrolo[1,2-c]oxazol-5(1H)-one (1.0 eq) in THF (3 vol) while maintaining the temperature at 60±5° C. The completion of reaction was monitored by HPLC every hour until the conversion >99% (system purity was 55%˜60%). The reaction mixture was then cooled to 15˜20° C., filtered and washed the cake with EtOAc (2 vol). The combined filtrate was washed with brine (3 vol) and the aqueous phase was back-extracted with EtOAc (3 vols). The combined organic phase was concentrated to about 3 vol under vacuum below 45° C. Add silica gel (1 wt/wt) and continued to concentrate to almost dryness. The solid residue was purified by silica gel (2 wt/wt) chromatography eluting with petroleum ether (PE) followed by EtOAc/PE=1:10 (v/v). The yield was about 40% (97.1% HPLC purity). ESI MS m/z (M+H)+ 230.16.

Workup

  1. temperatureCooled to 10˜20° C.
  2. temperatureCooled down back to 10˜20° C.
  3. temperaturewhile maintaining the temperature at 60±5° C
  4. customThe completion of reaction
  5. waitwas monitored by HPLC every hour until the conversion >99% (system purity was 55%˜60%)
  6. temperatureThe reaction mixture was then cooled to 15˜20° C.
  7. filtrationfiltered
  8. washwashed the cake with EtOAc (2 vol)
  9. washThe combined filtrate was washed with brine (3 vol)
  10. extractionthe aqueous phase was back-extracted with EtOAc (3 vols)
  11. concentrationThe combined organic phase was concentrated to about 3 vol under vacuum below 45° C
  12. concentrationto concentrate to almost dryness
  13. customThe solid residue was purified by silica gel (2 wt/wt) chromatography
  14. washeluting with petroleum ether (PE)

Sources & evidence

ORD record
ord-de60463000094a8dbf58f907aa4d017d
Source dataset
uspto-grants-2014_12
Patent number
US08921573B2

Reaction notes

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