Potassium Phosphate, Tribasic → 3-(5-Cyclopent-2-enyl-1H-inden-2-ylmethoxy)-2,6-difluoro-benzamide

HRID 538595Notes

Reaction equation

HRID 538595 reaction equation
[F:1][C:2]1[C:10]([O:11][CH2:12][C:13]2[CH2:14][C:15]3[C:20]([CH:21]=2)=[CH:19][C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=3)=[CH:9][CH:8]=[C:7]([F:31])[C:3]=1[C:4]([NH2:6])=[O:5].[C:32]1(OS(C(F)(F)F)(=O)=O)[CH2:36][CH2:35][CH2:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O>[CH:36]1([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C:13]([CH2:12][O:11][C:10]2[C:2]([F:1])=[C:3]([C:7]([F:31])=[CH:8][CH:9]=2)[C:4]([NH2:6])=[O:5])=[CH:21]3)[CH2:35][CH2:34][CH:33]=[CH:32]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 11769877Trifluoro-methanesulfonic acid cyclopent-1-enyl esterHCID 666197492,6-Difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-inden-2-ylmethoxy]-benzamide

Product 1

HCID 666197953-(5-Cyclopent-2-enyl-1H-inden-2-ylmethoxy)-2,6-difluoro-benzamideYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2,6-Difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-inden-2-ylmethoxy]-benzamide (0.25 g, 0.56 mmol) in 7 ml of anhydrous DMF and water (3.5 ml) was added trifluoromethanesulfonic acid cyclopent-1-enyl ester (0.37 g, 1.70 mmol) and potassium phosphate (0.14 g, 0.60 mmol). The reaction mixture was degassed for 10 minutes followed by addition of dichlorobis(triphenyl phosphine) palladium (II) (0.05 g, 0.08 mmol). The reaction mixture was heated at 80° C. for 1 h under the nitrogen atmosphere. After the completion of the reaction mixture (TLC monitoring), water (25 mL) was added and extracted with ethyl acetate (3×50 mL). The combined organics was washed with water, brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified over silica gel (230-400 M, 45% EtOAc-Hexane) to get the desired product (0.14 g, 65%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ 1.22 (m, 2H), 2.01 (m, 2H), 2.88 (m, 2H), 5.68 (s, 2H), 6.43 (s, 1H), 7.01 (t, J=9.20 Hz, 1H), 7.37 (m, 1H), 7.67 (d, J=8.40 Hz, 1H), 7.89 (br s, 1H), 7.94 (s, 1H), 8.07 (d, J=8.40 Hz, 1H) and 8.18 (br s, 1H). MS ES+ (387.15), HPLC (method II) Rt=13.74 min.

Workup

  1. customThe reaction mixture was degassed for 10 minutes
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organics was washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified over silica gel (230-400 M, 45% EtOAc-Hexane)

Sources & evidence

ORD record
ord-b6d1d589215741628530e960015f0520
Source dataset
uspto-grants-2014_10
Patent number
US08865736B2

Reaction notes

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