Sodium Carbonate → 5-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenyl}-nicotinic acid methyl ester

HRID 2096874Notes

Reaction equation

HRID 2096874 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[CH:17]([CH3:35])[C:18]([C:24]1[CH:25]=[CH:26][C:27]2[O:31][C:30](=[O:32])[N:29]([CH3:33])[C:28]=2[CH:34]=1)([OH:23])[C:19]([F:22])([F:21])[F:20].[CH3:36][O:37][C:38]([C:40]1[CH:41]=[N:42][CH:43]=[C:44](Br)[CH:45]=1)=[O:39].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2]>[CH3:36][O:37][C:38](=[O:39])[C:40]1[CH:45]=[C:44]([C:6]2[CH:5]=[CH:4][C:3]([CH:17]([CH3:35])[C:18]([OH:23])([C:24]3[CH:25]=[CH:26][C:27]4[O:31][C:30](=[O:32])[N:29]([CH3:33])[C:28]=4[CH:34]=3)[C:19]([F:20])([F:21])[F:22])=[C:2]([Cl:1])[CH:7]=2)[CH:43]=[N:42][CH:41]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 699336Methyl 5-bromopyridine-3-carboxylateHCID 66697095HCID 66697095, compound

Product 1

HCID 666970175-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenyl}-nicotinic acid methyl esterYield 52%

Reagents, catalysts & solvents 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

5-{2-[2-Chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1-hydroxy-1-trifluoromethyl-propyl}-3-methyl-3H-benzooxazol-2-one (200 mg, obtained in Example 186, step 1), methyl-5-bromopyridine-3-carboxylate (169 mg, [CAS Reg. No. 29681-44-5]) and dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II)dichloromethane adduct (29 mg) were dissolved in dioxane (5 mL) and water (1.7 mL). To the reaction mixture was added 2.0 M aqueous Na2CO3 (0.29 mL). The mixture was heated to 65° C. over night. The reaction mixture was cooled, poured into ice/water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a colorless foam (110 mg, 52%). MS (m/e)=521.1 [M+H+].

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-54e0eccf58a445e8a68fc377c836d345
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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