Sodium Carbonate → 6-{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 2096828ノート

反応式

HRID 2096828 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([C:15]2[CH:16]=[CH:17][C:18]3[O:22][C:21](=[O:23])[N:20]([CH3:24])[C:19]=3[CH:25]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:27])[CH:3]=1.C([O-])(=O)C.[K+].[CH3:33][O:34][C:35](=[O:43])[C:36]1[CH:41]=[CH:40][C:39](Cl)=[N:38][CH:37]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[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].O>[CH3:33][O:34][C:35](=[O:43])[C:36]1[CH:41]=[CH:40][C:39]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([OH:14])([C:15]3[CH:16]=[CH:17][C:18]4[O:22][C:21](=[O:23])[N:20]([CH3:24])[C:19]=4[CH:25]=3)[C:10]([F:13])([F:11])[F:12])=[C:4]([Cl:27])[CH:3]=2)=[N:38][CH:37]=1

参加物

9

反応物 4

HCID 10340Sodium CarbonateHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 517044Potassium AcetateHCID 666969815-[2-(4-Bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one

生成物 1

HCID 666970026-{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収率 24%

試薬・触媒・溶媒 4

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

5-[2-(4-Bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one (130 mg, obtained in Example 116, step 8), bis-(pinacolato)-diboron (78 mg), potassium acetate (82 mg) and bis-(triphenylphosphine)-palladium(II)-dichloride (6 mg) was dissolved in dioxane (6 mL). The reaction mixture was heated to 100° C. for 2.5 hours. The reaction mixture was cooled to r.t. and water (1 mL), methyl-6-chloronicotinate (96 mg, [CAS Reg. No. 73781-91-6]), dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium (II) dichloromethane adduct (20 mg) and 2.0 M aqueous Na2CO3 (0.21 mL) were added and the mixture was heated to 65° C. over night. The reaction mixture was cooled, poured into ice/water and extracted two 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 (35 mg, 24%). MS (m/e)=521.3 [M+H+].

後処理

  1. temperatureThe reaction mixture was cooled to r.t.
  2. temperaturethe mixture was heated to 65° C. over night
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted two times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

出典と根拠

ORDレコード
ord-c9c2b3f0f0564b35bfcdd3ca90b3b8bc
出典データセット
uspto-grants-2013_05
特許番号
US08450313B2

反応ノート

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