Cesium carbonate → 3'-({[4-Bromo-1-(2,2-dimethylpropyl)-1H-benzotriazol-5-yl]oxy}methyl)-5-fluorobiphenyl-3-carboxylic acid

HRID 1626965Notes

Reaction equation

HRID 1626965 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][CH2:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.Br[C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([F:37])[CH:36]=1)[C:31]([OH:33])=[O:32].C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][CH2:17][C:18]1[CH:19]=[C:20]([C:28]2[CH:36]=[C:35]([F:37])[CH:34]=[C:30]([C:31]([OH:33])=[O:32])[CH:29]=2)[CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27733393-Bromo-5-fluorobenzoic acidHCID 67888636[3-({[4-Bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-yl]oxy}methyl)phenyl]boronic acid

Product 1

HCID 676071923'-({[4-Bromo-1-(2,2-dimethylpropyl)-1H-benzotriazol-5-yl]oxy}methyl)-5-fluorobiphenyl-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 178478232Dichloro 1,1'-bis(diphenylphosphino)ferrocene palladiumCatalyst

Procedure

[3-({[4-Bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-yl]oxy}methyl)phenyl]boronic acid (3-1) (400 mg, 0.957 mmol, 1.0 equiv.), 3-bromo-5-fluorobenzoic acid (12) (800 mg, 3.65 mmol, 3.8 equiv.) and dichloro[1,1′-bis (diphenylphosphino) ferrocene] palladium II dichloromethane adduct (78 mg, 0.096 mmol, 0.1 equiv.) were dissolved in anhydrous degassed 1,4-dioxane (8 mL), then treated with a 1 M aqueous solution of cesium carbonate (5.2 mL, 5.3 mmol, 5.5 equiv.). The reaction mixture was irradiated in microwavereactor at 150° C. for 10 minutes. The mixture was concentrated in vacuo and purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA present) to afford Example 3-2. 1H NMR δ (CDCl3): 8.15 (s, 1H), 7.77 (s, 2H), 7.58-7.52 (m, 4H), 7.41 (d, 1H, J=8.5 Hz), 7.29 (d, 1H, J=9.0 Hz), 5.32 (s, 2H), 4.38 (s, 2H), 1.04 (s, 9H) ppm. LRMS m/z (M+H) 512.0 and 514.0 (intensity ratio ˜1:1) found, 512.1 and 514.1 required.

Workup

  1. customin anhydrous degassed 1,4-dioxane (8 mL)
  2. customThe reaction mixture was irradiated in microwavereactor at 150° C. for 10 minutes
  3. concentrationThe mixture was concentrated in vacuo
  4. custompurified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA present)
  5. customto afford Example 3-2

Sources & evidence

ORD record
ord-b6cd1ccffbb24e0589fd0393bb95eeba
Source dataset
uspto-grants-2014_07
Patent number
US08785481B2

Reaction notes

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