Toluene → HCID 59750894, compound

HRID 748773Notes

Reaction equation

HRID 748773 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4]C)C.C1C=CC([O:14]P(OC2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.C1(C)C=CC=CC=1.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([S:41]([CH:44]([C:51]2[CH:56]=[C:55]([F:57])[CH:54]=[CH:53][C:52]=2[F:58])[CH2:45]CCC(O)=O)(=[O:43])=[O:42])=[CH:37][CH:36]=1.[CH3:59][C:60]([OH:63])([CH3:62])[CH3:61]>ClCCl.CCCCCC>[Cl:34][C:35]1[CH:36]=[CH:37][C:38]([S:41]([CH:44]([C:51]2[CH:56]=[C:55]([F:57])[CH:54]=[CH:53][C:52]=2[F:58])[CH2:45][CH2:7][CH2:6][NH:3][C:4](=[O:14])[O:63][C:60]([CH3:62])([CH3:61])[CH3:59])(=[O:43])=[O:42])=[CH:39][CH:40]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 59750943HCID 59750943, compound

Product 1

HCID 59750894HCID 59750894, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

Under a nitrogen atmosphere, triethylamine (126 μl, 0.907 mmol) and diphenylphosphoric azide (195 μl, 0.907 mmol) were added to a toluene solution (6 ml) of the 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-difluorophenyl)valeric acid (294 mg, 0.533 mmol) obtained in Example 202. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was heated under reflux for 3 hours. After cooling to room temperature and addition of 2-methyl-2-propanol (1 ml), the mixture was stirred at 80° C. for further 18 hours. The reaction mixture was then concentrated and the residue thus obtained was dissolved in dichloromethane. The resulting solution was washed successively with a saturated aqueous solution of potassium bicarbonate, water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated to yield the title compound (171 mg, 0.383 mmol, 51%) as a white solid. The solid thus obtained was recrystallized from ethyl acetate-hexane, whereby colorless needle crystals were obtained.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperatureAfter cooling to room temperature
  4. stirringthe mixture was stirred at 80° C. for further 18 hours
  5. concentrationThe reaction mixture was then concentrated
  6. customthe residue thus obtained
  7. washThe resulting solution was washed successively with a saturated aqueous solution of potassium bicarbonate, water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue thus obtained
  11. concentrationethyl acetate=4:1 eluate was concentrated

Sources & evidence

ORD record
ord-7e250ca3a1794b4ca4e3368bc22d522b
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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