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

HRID 415667Notes

Reaction equation

HRID 415667 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)[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O>[C:32]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)[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 3194401-Cyclohexenyl trifluoromethanesulfonateHCID 666197492,6-Difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-inden-2-ylmethoxy]-benzamide

Product 1

HCID 666197163-(5-Cyclohex-1-enyl-1H-inden-2-ylmethoxy)-2,6-difluoro-benzamideYield 22.3%

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 (0.10 g, 0.20 mmol) in 3 ml of anhydrous DMF and water (1.5 ml) was added trifluoromethanesulfonic acid cyclohex-1-enyl ester (0.15 g, 0.60 mmol) and potassium phosphate (0.057 g, 0.20 mmol). The reaction mixture was degassed for 10 minutes followed by addition of dichlorobis(triphenyl phosphine) palladium (II) (0.02 g, 0.03 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 (0.017 g, 19%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ 1.63 (m, 4H), 2.20 (m, 2H), 2.45 (m, 2H), 5.67 (s, 2H), 6.29 (m, 1H), 7.12 (m, 1H), 7.37 (m, 1H), 7.57 (m, 2H), 7.90 (br s, 1H), 8.03 (d, J=8.40 Hz, 1H) and 8.18 (br s, 1H). MS ES+ (401.16), HPLC (method II) Rt=14.13 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-a68201227f454d45bb7172efec109137
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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