Tetrahydrofuran → HCID 58187754, compound

HRID 2369847Notes

Reaction equation

HRID 2369847 reaction equation
[F:1][C@H:2]1[CH2:18][C@@H:17]2[C@:9]([F:25])([C@@H:10]([OH:24])[CH2:11][C@@:12]3([CH3:23])[C@H:16]2[CH2:15][CH:14]=[C:13]3[C:19](=[O:22])[CH2:20]O)[C@:8]2([CH3:26])[C:3]1=[CH:4][C:5](=[O:27])[CH:6]=[CH:7]2.CCN(C(C)C)C(C)C.[F-:37].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(#N)C>[F:1][C@H:2]1[CH2:18][C@@H:17]2[C@:9]([F:25])([C@@H:10]([OH:24])[CH2:11][C@@:12]3([CH3:23])[C@H:16]2[CH2:15][CH:14]=[C:13]3[C:19](=[O:22])[CH2:20][F:37])[C@:8]2([CH3:26])[C:3]1=[CH:4][C:5](=[O:27])[CH:6]=[CH:7]2

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 2724141Tetrabutylammonium FluorideHCID 58187768HCID 58187768, compound

Product 1

HCID 58187754HCID 58187754, compoundYield 61.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a nitrogen atmosphere, intermediate 3 (100 mg, 0.264 mmol) was dissolved in acetonitrile (4 ml), and Mesyl-Cl (32 μl, 0.411 mmol) and DIPEA (78 μl, 0.447 mmol) were added. The mixture was stirred at RT for 30 minutes. Potassium fluoride (154 mg, 2.64 mmol) was added, and the mixture was stirred for 1 h at 60° C. TBAF 1M in THF (529 μl, 0.529 mmol) was added, and the mixture is stirred at 60° C. for 4 hours. The reaction mixture was partitioned between water and AcOEt, the organic layer was separated, dried over Na2SO4 and concentrated. The crude was purified by silica gel flash chromatography (eluent DCM/AcOEt=1:1) to yield intermediate 28 (62 mg, 61.7% yield).

Workup

  1. stirringthe mixture was stirred for 1 h at 60° C
  2. stirringthe mixture is stirred at 60° C. for 4 hours
  3. customThe reaction mixture was partitioned between water and AcOEt
  4. customthe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude was purified by silica gel flash chromatography (eluent DCM/AcOEt=1:1)

Sources & evidence

ORD record
ord-571e1c412f3f4db4a97fc10b38f6f4af
Source dataset
uspto-grants-2014_04
Patent number
US08710037B2

Reaction notes

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