(4-Carboxybutyl)triphenylphosphonium bromide → HCID 57857014, compound

HRID 561734Notes

Reaction equation

HRID 561734 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].[CH3:28][C:29](C)([O-])C.[K+].[F:34][C:35]([F:62])([CH2:54][O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[CH2:36][CH2:37][C@@H:38]1[C@@H:45]2[C@@H:41](OC(O)C2)[CH2:40][C@H:39]1[O:47][CH:48]1[CH2:53][CH2:52][CH2:51][CH2:50][O:49]1.[OH:63]S([O-])(=O)=O.[K+]>C1COCC1.[Cl-].[Na+].O>[F:62][C:35]([F:34])([CH2:54][O:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[CH2:36][CH2:37][C@H:38]1[C@H:39]([O:47][CH:48]2[CH2:53][CH2:52][CH2:51][CH2:50][O:49]2)[CH2:40][C@H:41]([OH:63])[C@@H:45]1[CH2:28]/[CH:29]=[CH:8]\[CH2:7][CH2:6][CH2:5][C:2]([OH:4])=[O:3]

Participants

7

Reactant 4

HCID 161236(4-Carboxybutyl)triphenylphosphonium bromideHCID 516920Potassium bisulfateHCID 23665647Potassium tert-butoxideHCID 57857073HCID 57857073, compound

Product 1

HCID 57857014HCID 57857014, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

4-Carboxybutyltriphenylphosphonium bromide (3.5 molar equivalents) is suspended in anhydrous THF under a nitrogen atmosphere. Potassium tert-butoxide in THF (1 M, 7 molar equivalents) is added dropwise to the white suspension. The reaction mixture becomes bright red over the course of the addition. The mixture continues stirring for 30 minutes at room temperature and is subsequently cooled to −15° C. in an ice/NaCl bath. The lactol ((3aR,4R,5R,6aS)-4-(3,3-difluoro-4-phenoxybutyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-ol) (limiting reagent, prepared in Step F) is dissolved in THF and added dropwise to the ylide. The reaction mixture becomes lighter orange in color. The mixture continues stirring for 2 hours at −15° C. and is subsequently allowed to warm to room temperature and stir overnight as the reaction mixture becomes dark red. The reaction mixture is acidified with 5% 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 ethyl acetate-hexane-acetic acid as eluent to afford the title intermediate.

Workup

  1. additionThe reaction mixture becomes bright red over the course of the addition
  2. temperatureis subsequently cooled to −15° C. in an ice/NaCl bath
  3. additionadded dropwise to the ylide
  4. stirringThe mixture continues stirring for 2 hours at −15° C.
  5. temperatureto warm to room temperature
  6. stirringstir overnight as the reaction mixture
  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-f1dc1fd465ff470e8f5ce7de56c4df50
Source dataset
uspto-grants-2011_11
Patent number
US08063240B2

Reaction notes

Loading…