Sodium Carbonate → (S)-3-(4-(2-bromo-5-fluoropyridin-4-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525410노트

반응식

HRID 525410 반응식
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]([CH3:20])([CH3:19])[O:10][C:9]2=[O:21])=[CH:4][CH:3]=1.[Br:22][C:23]1[CH:28]=[C:27](B(O)O)[C:26]([F:32])=[CH:25][N:24]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Br:22][C:23]1[CH:28]=[C:27]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C@@H:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11]([CH3:20])([CH3:19])[O:10][C:9]3=[O:21])=[CH:4][CH:3]=2)[C:26]([F:32])=[CH:25][N:24]=1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 44631046(2-Bromo-5-fluoropyridin-4-yl)boronic acid3회HCID 89813884(S)-3-(4-iodophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one2회

생성물 1

HCID 89813900(S)-3-(4-(2-bromo-5-fluoropyridin-4-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one수율 28%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매3회HCID 962Water용매

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온도
100 °C

실험 절차

A microwave vial was charged with (S)-3-(4-iodophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (Intermediate C)(0.200 g, 0.509 mmol), 2-bromo-5-fluoropyridine-4-boronic acid (commercially available from Combi Blocks, San Diego, Calif.) (0.224 g, 1.017 mmol), sodium carbonate (0.162 g, 1.526 mmol), dioxane (3.0 mL), and water (0.60 mL). Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) (DCM adduct)(0.042 g, 0.051 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture was then stirred at 100° C. in the microwave for 1 hour. Additional 2-bromo-5-fluoropyridine-4-boronic acid (0.224 g, 1.017 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (0.042 g, 0.051 mmol) were added, the system was purged with argon, and the tube was sealed. The resulting mixture was then stirred at 100° C. in a microwave for 1 hour. Additional 2-bromo-5-fluoropyridine-4-boronic acid (0.224 g, 1.017 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (0.042 g, 0.051 mmol) were added, the system was purged with argon, and the tube was sealed. The resulting mixture was stirred at 100° C. in a microwave for 1 hour. The reaction mixture was then filtered through Celite® brand filter aid and the filtrate was concentrated to afford a dark brown oil. The oil thus obtained was purified using column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-50% EtOAc-hexane) to afford (S)-3-(4-(2-bromo-5-fluoropyridin-4-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.062 g, 0.140 mmol, 28% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3H), 1.65 (s, 3H), 5.53 (s, 1H), 7.17-7.49 (m, 5H), 7.59-7.73 (m, 4H), 7.83 (d, J=5.97 Hz, 1H), 8.48 (d, J=2.35 Hz, 1H). m/z (ESI) 441 (M+H)+.

후처리

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. customthe system was purged with argon
  4. customthe tube was sealed
  5. stirringThe resulting mixture was then stirred at 100° C. in a microwave for 1 hour
  6. customthe system was purged with argon
  7. customthe tube was sealed
  8. stirringThe resulting mixture was stirred at 100° C. in a microwave for 1 hour
  9. filtrationThe reaction mixture was then filtered through Celite® brand
  10. filtrationfilter aid
  11. concentrationthe filtrate was concentrated
  12. customto afford a dark brown oil
  13. customThe oil thus obtained
  14. customwas purified

출처 및 근거

ORD 기록
ord-0f597457a60141269a739a540fef6780
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340549B2

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