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 2096828노트

반응식

HRID 2096828 반응식
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

참가 물질

9

반응물 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

생성물 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 ester수율 24%

시약·촉매·용매 4

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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+].

후처리

  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)

출처 및 근거

ORD 기록
ord-c9c2b3f0f0564b35bfcdd3ca90b3b8bc
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450313B2

반응 노트

불러오는 중…