Nitrogen → 4-[5-Chloro-4-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-(methyl-o-tolyl-carbamoyl)-phenoxy]-butyric acid tert-butyl ester

HRID 1485968Notes

Reaction equation

HRID 1485968 reaction equation
[C:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14](B2OC(C)(C)C(C)(C)O2)=[CH:13][C:12]=1[C:27](=[O:37])[N:28]([CH3:36])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35])([CH3:4])([CH3:3])[CH3:2].Br[C:40]1[C:45]([C:46]#[N:47])=[CH:44][C:43]([C:48]([F:51])([F:50])[F:49])=[N:42][CH:41]=1.C([O-])([O-])=O.[Na+].[Na+].N#N>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([C:40]2[CH:41]=[N:42][C:43]([C:48]([F:51])([F:50])[F:49])=[CH:44][C:45]=2[C:46]#[N:47])=[CH:13][C:12]=1[C:27](=[O:37])[N:28]([CH3:36])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 569733155-Bromo-2-(trifluoromethyl)isonicotinonitrileHCID 686022774-[5-Chloro-2-(methyl-o-tolyl-carbamoyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-butyric acid tert-butyl ester

Product 1

HCID 686031324-[5-Chloro-4-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-(methyl-o-tolyl-carbamoyl)-phenoxy]-butyric acid tert-butyl esterYield 99.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-[5-Chloro-2-(methyl-o-tolyl-carbamoyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-butyric acid tert-butyl ester (444.0 mg, 0.8 mmol), 5-bromo-2-trifluoromethyl-isonicotinonitrile (171.0 mg, 0.7 mmol), Pd(Ph3P)4 (78.6 mg, 0.07 mmol), Na2CO3 (432.0 mg, 4.1 mmol) in dioxane (9 mL) and water (1 mL) was degassed with N2 for 5 min, sealed, and heated at 100° C. for 12 hrs. The mixture was then partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over MgSO4 and filtered. Concentration and purification by TLC plates eluting with ethyl acetate in hexanes (2/3) and again with TLC plates eluting with acetonitrile/dichloromethane (1/9) gave 4-[5-chloro-4-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-(methyl-o-tolyl-carbamoyl)-phenoxy]-butyric acid tert-butyl ester (410 mg). MS: 588.7 (M+H)+; tR=11.05 min (method 3).

Workup

  1. customsealed
  2. customThe mixture was then partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationConcentration and purification by TLC plates
  7. washeluting with ethyl acetate in hexanes (2/3) and again with TLC plates
  8. washeluting with acetonitrile/dichloromethane (1/9)

Sources & evidence

ORD record
ord-90d155467b404a6992ee1ca8d0bf670c
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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