Tributylphosphine → HCID 491350, compound

HRID 843131Notes

Reaction equation

HRID 843131 reaction equation
[CH3:1][C:2]1[C:6]2[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH2:23][OH:24].C(P(CCCC)CCCC)CCC.[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1O.C([O-])(O)=O.[Na+]>C1COCC1>[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1[O:24][CH2:23][C:3]1[O:4][C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[C:6]=2[C:2]=1[CH3:1]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 1230512,4-DifluorophenolHCID 516892Sodium BicarbonateHCID 22615037HCID 22615037, compound

Product 1

HCID 491350HCID 491350, compoundYield 40.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the compound in Example 11 (65 mg), tributylphosphine (61 mg) and 2,4-difluorophenol (26 mg) in THF (1 ml) was added bispiperidine azodicarboxyl amide (76 mg) in THF (0.5 ml) at −45° C. under argon atmosphere, and the mixture was slowly warmed up to room temperature over 18 hoursi period. The mixture was poured into sat. NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4. After filtration, the solvent was removed under reduced pressure and the residue was chromatographed on silica gel (dichloromethane/methanol) to give a yellow oil (35 mg, 40%). ESIMS: m/z 439 (MH+); 1H-NMR (CDCl3): δ 2.07 (2H, tt, J=6.9 Hz, 5.9 Hz, CH2), 2.27 (3H, s, CH3), 2.89 (2H, t, J=6.9 Hz, NCH2), 3.83 (2H, s, NCH2), 4.13 (2H, t, J=5.9 Hz, OCH2), 5.10 (2H, s, OCH2), 6.59 (1H, d, J=7.9 Hz, Ar—H), 6.71-7.23 (6H, m, 6×Ar—H), 7.66 (1H, dd, J=1.7 Hz, 7.9 Hz, Ar—H), 8.49 (1H, d, J=4.9 Hz, Ar—H), 8.56 (1H, s, Ar—H).

Workup

  1. customat −45° C.
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration
  6. customthe solvent was removed under reduced pressure
  7. customthe residue was chromatographed on silica gel (dichloromethane/methanol)

Sources & evidence

ORD record
ord-9090412ea88b4e059e2a3bef38944ffa
Source dataset
uspto-grants-2002_04
Patent number
US06376491B1

Reaction notes

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