Tetrahydrofuran → Methyl 3-[(e)-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-1-(4-fluorobenzoyl)-4-phenyl-3-butenyl]benzoate

HRID 1371031Notes

Reaction equation

HRID 1371031 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([CH:8]([C:18]2[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=2)[C:21]([O:23][CH3:24])=[O:22])[CH2:9]/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:7])=[CH:4][CH:3]=1.[CH2:30]1OCCOCCOCCOCCOCCOC1.[CH3:48][C:49]([O-:52])([CH3:51])[CH3:50].[K+].C([C:58]1[C:59](C(C)(C)C)=[C:60]([C:66]([P:69](=[O:72])([O-:71])[O-])([F:68])[F:67])[CH:61]=[CH:62][C:63]=1[CH2:64]Br)(C)(C)C.[CH2:77]1[CH2:81]OC[CH2:78]1>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[C:49]([O:52][P:69]([C:66]([F:67])([F:68])[C:60]1[CH:59]=[CH:58][C:63]([CH2:64][C:8]([C:18]2[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=2)[C:21]([O:23][CH3:24])=[O:22])([C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:29][CH:28]=2)[CH2:9]/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:62][CH:61]=1)([O:71][C:77]([CH3:78])([CH3:81])[CH3:30])=[O:72])([CH3:51])([CH3:50])[CH3:48]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 2855718-Crown-6HCID 18510225Methyl 3-[(e)-1-(4-fluorobenzoyl)-4-phenyl-3-butenyl]benzoateHCID 23665647Potassium tert-butoxideHCID 131723939Di (tert-butyl)[4-(bromomethyl)phenyl](difluoro)methylphosphonate

Product 1

HCID 18510242Methyl 3-[(e)-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-1-(4-fluorobenzoyl)-4-phenyl-3-butenyl]benzoate

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

To a degassed solution of the product from Step 2 (0.30 g, 0.77 mmol), 18-Crown-6 (102 mg, 0.39 mmol), and Bu4NI (28 mg, 0.077 mmol) in THF at −78° C. was added the KOtBu solution. After 15 min. at −78° C., a solution of di(tert-butyl)(4-(bromomethyl)phenyl)(difluoro)methyl phosphonate (Example 1, Step 7) (319 mg, 0.77 mmol) in THF (3 mL) via double-tipped needle. The cold bath was removed and the reaction was stirred at r.t. for 1.5 h. Saturated NH4Cl solution was then added and the product was extracted with EtOAc. The organic layer was washed with H2O and brine, and was then dried (MgSO4), filtered, and evaporated. The residue was purified by flash chromatography (1:20 Et2O: toluene, 1% Et3N) to give an oil (98 mg).

Workup

  1. customThe cold bath was removed
  2. additionSaturated NH4Cl solution was then added
  3. extractionthe product was extracted with EtOAc
  4. washThe organic layer was washed with H2O and brine
  5. dry with materialwas then dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography (1:20 Et2O: toluene, 1% Et3N)

Sources & evidence

ORD record
ord-279c2c56c4ab4625a46dba04e9d9cb9c
Source dataset
uspto-grants-2003_06
Patent number
US06583126B2

Reaction notes

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