Cesium fluoride → (Z)-3-Cyclohexyl-2-(5-methanesulfonyl-thiophen-2-yl)-prop-2-en-1-ol

HRID 2103612Notes

Reaction equation

HRID 2103612 reaction equation
BrC1SC(S(C)(=O)=O)=CC=1.[F-].[Cs+].C1(C=C(B2OC(C)(C)C(C)(C)O2)CO)CCCCC1.[CH:32]1(/[CH:38]=[C:39](\[C:42]2[S:43][C:44]([S:47]([CH3:50])(=[O:49])=[O:48])=[CH:45][CH:46]=2)/[CH:40]=[O:41])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.[BH4-].[Na+]>O1CCOCC1.CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH:32]1(/[CH:38]=[C:39](\[C:42]2[S:43][C:44]([S:47]([CH3:50])(=[O:49])=[O:48])=[CH:45][CH:46]=2)/[CH2:40][OH:41])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

10

Reactant 5

HCID 25953Cesium fluorideHCID 4311764Sodium borohydrideHCID 173902812-Bromo-5-methanesulfonylthiopheneHCID 670845993-Cyclohexyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-prop-2-en-1-olHCID 86605125(Z)-3-cyclohexyl-2-(5-methanesulfonyl-thiophen-2-yl)-propenal2×

Product 1

HCID 69058010(Z)-3-Cyclohexyl-2-(5-methanesulfonyl-thiophen-2-yl)-prop-2-en-1-ol

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Add 2-bromo-5-methanesulfonyl-thiophene (2.26 g, 9.39 mmol), caesium fluoride ( 2.85 g, 18.78 mmol) and tetrakis-(triphenylphosphin)-palladium(0) (543 mg, 0.47 mmol) to a solution of 3-cyclohexyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-prop-2-en-1-ol (2.5 g, 9.39 mmol) in dioxane (50 mL). Stir at 80° C. for 24 h, monitor completion of the reaction by LCMS. Treat the reaction mixture with water and extract with dichloromethane. Dry organic layers over sodium sulfate and remove solvents under vacuum to obtain 4.85 g crude product. Purify by siliga gel chromatography, eluting with gradient from 10:0 to 7:3 hexane:ethyl acetate. 690 mg isolated product was (Z)-3-cyclohexyl-2-(5-methanesulfonyl-thiophen-2-yl)-propenal. MS (m/e): 299.0 (M+H). Add a solution of (Z)-3-cyclohexyl-2-(5-methanesulfonyl-thiophen-2-yl)-propenal (690 mg, 2.31 mmol) in methanol (2 mL) to a suspension of NaBH4 in methanol (3 mL) at 0° C. and stir for 1 h, monitor completion of the reaction by LCMS. Dilute reaction mixture with water, extract with ethyl acetate, wash combined organic layers with water and saturated sodium chloride, dry over sodium sulfate and remove solvent under vacuum to obtain 704 mg crude product. MS (m/e): 301.0 (M+H).

Workup

  1. customcompletion of the reaction by LCMS
  2. extractionextract with dichloromethane
  3. customDry organic layers over sodium sulfate and remove solvents under vacuum
  4. customto obtain 4.85 g crude product
  5. customPurify by siliga gel chromatography
  6. washeluting with gradient from 10:0 to 7:3 hexane
  7. custom690 mg isolated product
  8. stirringstir for 1 h
  9. customcompletion of the reaction by LCMS
  10. additionDilute
  11. extractionextract with ethyl acetate
  12. washwash
  13. dry with materialdry over sodium sulfate
  14. customremove solvent under vacuum

Sources & evidence

ORD record
ord-c276c70d98de4eefae9c4998267d41a7
Source dataset
uspto-grants-2009_08
Patent number
US07576108B2

Reaction notes

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