Sodium Carbonate → HCID 58959992, compound

HRID 916006Notes

Reaction equation

HRID 916006 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[CH2:5][C:6]([OH:24])([CH2:11][C:12]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])([CH3:14])[CH3:13])[C:7]([F:10])([F:9])[F:8].B1([C:34]2[CH:39]=[CH:38][CH:37]=[N:36][CH:35]=2)OCCCO1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.[OH-].[NH4+]>[F:10][C:7]([F:8])([F:9])[C:6]([CH2:5][C:4]1[CH:25]=[CH:26][CH:27]=[C:2]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH:3]=1)([OH:24])[CH2:11][C:12]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 10310475HCID 10310475, compound

Product 1

HCID 58959992HCID 58959992, compoundYield 73.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A mixture of 50 mg (0.11 mmol) of 2-(3-bromobenzyl)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-ol, 98 mg (0.60 mmol) of pyridine-3-boronic acid 1,3-propanediol cyclic ester, and 28 mg (0.02 mmol) of Pd[P(Ph)3]4 in 4 mL of toluene, 2 mL of EtOH, and 1 mL of 2 M aqueous sodium carbonate was warmed to reflux for 20 hours. The reaction mixture was then cooled and diluted with 5 mL of 12% aqueous ammonium hydroxide and extracted with three 5 mL portions of EtOAc. The combined organic layers were washed with three 5 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using hexanes with a few drops of dichloromethane to load the sample and then eluted with EtOAc-hexanes (1:99, then 3:97, then 1:9) to afford 36 mg (72%) of a white solid. Recrystallization from ether/hexanes gave 28 mg of the title compound as a crystalline material, m.p. 148° C.-150° C.

Workup

  1. temperaturewas warmed
  2. temperatureto reflux for 20 hours
  3. temperatureThe reaction mixture was then cooled
  4. extractionextracted with three 5 mL portions of EtOAc
  5. washThe combined organic layers were washed with three 5 mL portions of brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was chromatographed on silica gel
  10. washeluted with EtOAc-hexanes (1:99

Sources & evidence

ORD record
ord-3ffa6e329d50421fa06bb257583dc35d
Source dataset
uspto-grants-2007_09
Patent number
US07268152B2

Reaction notes

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