Sodium Iodide → HCID 57428858, compound

HRID 2267412Notes

Reaction equation

HRID 2267412 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[S:11][CH:12]=[CH:13][C:14]=2[CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)O)=[CH:4][CH:3]=1.C[Si](I)(C)C.[I-].[Na+].Cl[Si](C)(C)C.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:10]2[S:11][CH:12]=[CH:13][C:14]=2[CH2:15][CH2:16][N:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 14798Sodium HydroxideHCID 85247Trimethylsilyl iodideHCID 60204545HCID 60204545, compound2×

Product 1

HCID 57428858HCID 57428858, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(4-Fluorophenyl)(3-(2-(pyrrolidin-1-yl)ethyl)thiophen-2-yl)methanol from step (ii) was reduced with trimethylsilyliodide in accordance with published procedure (See reference: Tetrahedron 1995, 51 (41), 11043-11062.) A dry three-necked flask equipped with an addition funnel and a nitrogen inlet was charged with sodium iodide (0.87 g, 5.8 mmol) and acetonitrile (5.0 mL). Then, chlorotrimethylsilane (0.73 mL, 5.8 mmol) was added via syringe and the reaction mixture was allowed to stir at ambient temperature for about 15 min. At that time, the bright yellow mixture was cooled to 0° C. and a solution of (4-fluorophenyl)(3-(2-(pyrrolidin-1-yl)ethyl)thiophen-2-yl)methanol (353 mg, 1.16 mmol) in acetonitrile (5 mL) was added dropwise over the course of an hour. The reaction mixture was allowed to warm to room temperature over 16 h and then cooled back down below 5° C. before work-up. A solution of NaOH (5 N, 1.5 mL, 7.5 mmol) was added and the reaction mixture cooled to rt before it was diluted with EtOAc and stirred for an additional 10 min. The layers were separated and the aqueous layer extracted with another portion of EtOAc. The combined organic layers were washed with a solution of saturated aqueous Na2S2O3.5H2O, water, and brine, dried over MgSO4, and concentrated. The resulting residue was purified by flash chromatography, eluting with 1-10% (0.5 M ammonia in MeOH)/dichloromethane to afford the product as a pale yellow oil (160 mg, 0.56 mmol, 48% yield). MS (M+H)+ 290.

Workup

  1. customequipped with an addition funnel and a nitrogen inlet
  2. temperatureAt that time, the bright yellow mixture was cooled to 0° C.
  3. temperatureto warm to room temperature over 16 h
  4. temperaturecooled back down below 5° C. before work-up
  5. temperaturethe reaction mixture cooled to rt before it
  6. stirringstirred for an additional 10 min
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted with another portion of EtOAc
  9. washThe combined organic layers were washed with a solution of saturated aqueous Na2S2O3.5H2O, water, and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe resulting residue was purified by flash chromatography
  13. washeluting with 1-10% (0.5 M ammonia in MeOH)/dichloromethane

Sources & evidence

ORD record
ord-720ff8bfe71c44c0ad66117d2e4c6347
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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