Tetrahydrofuran → HCID 57857034, compound

HRID 561742Notes

Reaction equation

HRID 561742 reaction equation
[Br-].[C:2]([CH2:5][CH2:6][CH2:7][CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:4])=[O:3].C[C:29]([CH3:32])([O-:31])[CH3:30].[K+].[S:34]1[C:38]([C@H:39]([O:52][Si:53]([C:66]([CH3:69])([CH3:68])[CH3:67])([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)/[CH:40]=[CH:41]/[C@@H:42]2[C@@H]3[C@@H](OC(O)C3)C[C@H:43]2[OH:51])=[CH:37][C:36]2[CH:70]=[CH:71][CH:72]=[CH:73][C:35]1=2.OS([O-])(=O)=O.[K+].[CH2:80]1COC[CH2:81]1>[Cl-].[Na+].O>[S:34]1[C:38]([C@H:39]([O:52][Si:53]([C:66]([CH3:69])([CH3:67])[CH3:68])([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)/[CH:40]=[CH:41]/[C@H:42]2[C@H:43]([OH:51])[CH2:32][C@H:29]([OH:31])[C@@H:30]2[CH2:80]/[CH:81]=[CH:8]\[CH2:7][CH2:6][CH2:5][C:2]([OH:4])=[O:3])=[CH:37][C:73]2[CH:72]=[CH:71][CH:70]=[CH:36][C:35]1=2

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 161236(4-Carboxybutyl)triphenylphosphonium bromideHCID 516920Potassium bisulfateHCID 23665647Potassium tert-butoxideHCID 57856997HCID 57856997, compound

Product 1

HCID 57857034HCID 57857034, compound

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

4-Carboxybutyltriphenylphosphonium bromide (3.5 molar equivalents) is suspended in anhydrous THF under a nitrogen atmosphere. Potassium tert-butoxide (1 M in THF, 7 molar equivalents) is added dropwise to the white suspension. The reaction mixture becomes bright red over the course of the addition and is subsequently stirred for 30 minutes at room temperature, then cooled to −15° C. in an ice/NaCl bath. The lactol (3aR,4R,5R,6aS)-4-((R,E)-3-(benzo[b]thiophen-2-yl)-3-(tert-butyldiphenylsilyloxy)prop-1-enyl)hexahydro-2H-cyclopenta[b]furan-2,5-diol (8a, limiting reagent) is dissolved in THF and added dropwise to the ylide. The reaction mixture becomes lighter orange in color and is additionally stirred for 2 hours at −15° C. and is then allowed to warm to room temperature and stir overnight. The reaction mixture becomes dark red. The reaction mixture is acidified with 5% aqueous KHSO4, diluted with brine (250 mL) and extracted with ethyl acetate (200 mL). The aqueous layer is extracted with another portion of ethyl acetate (50 mL) and the combined organic extracts are washed twice with brine (250 mL), dried over sodium sulfate, and evaporated to yield crude product. The crude product is purified by flash chromatography on regular silica gel using hexanes-ethyl acetate with 0.4% acetic acid as eluent to afford the title intermediate 9a.

Workup

  1. additionThe reaction mixture becomes bright red over the course of the addition
  2. temperaturecooled to −15° C. in an ice/NaCl bath
  3. additionadded dropwise to the ylide
  4. stirringis additionally stirred for 2 hours at −15° C.
  5. temperatureto warm to room temperature
  6. stirringstir overnight
  7. extractionextracted with ethyl acetate (200 mL)
  8. extractionThe aqueous layer is extracted with another portion of ethyl acetate (50 mL)
  9. washthe combined organic extracts are washed twice with brine (250 mL)
  10. dry with materialdried over sodium sulfate
  11. customevaporated
  12. customto yield crude product
  13. customThe crude product is purified by flash chromatography on regular silica gel

Sources & evidence

ORD record
ord-a029c9437bdd4990b6c18b5d5caee0f5
Source dataset
uspto-grants-2011_11
Patent number
US08063240B2

Reaction notes

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