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Toluene → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4'-fluoro-5'-isopropyl-2'-methoxy-4-nitrobiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1028660
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HRID 1028660 반응식
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:30])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1(C)C=CC=CC=1.[F:40][C:41]1[C:46]([CH:47]([CH3:49])[CH3:48])=[CH:45][C:44](B(O)O)=[C:43]([O:53][CH3:54])[CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)C>[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:21]=3[C:44]3[CH:45]=[C:46]([CH:47]([CH3:49])[CH3:48])[C:41]([F:40])=[CH:42][C:43]=3[O:53][CH3:54])[C@H:14]2[CH3:30])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 86603442(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one

생성물 1

HCID 11527347(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4'-fluoro-5'-isopropyl-2'-methoxy-4-nitrobiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 702Ethanol용매HCID 962Water용매

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온도
90 °C

실험 절차

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one (3.877 g, 7.35 mmol) in a toluene (24 mL): ethanol (12 mL): water (6 mL) mixture was added (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (2.337 g, 11.03 mmol), tetrakis (triphenylphosphine) palladium(0) (425 mg, 5 mol %) and sodium carbonate (1.56 g, 14.72 mmol). The resulting mixture was bubbled with nitrogen and then heated in a 90° C. oil bath for 10 h. An aliquot showed complete consumption of the starting material. The reaction was quenched with brine. The resulting mixture was extracted with EtOAc and dried over Na2SO4. The resulting glassy mixture was purified by SiO2 (Biotage 40S cartridge, EtOAc/hexane, gradient). The titled compound was obtained as a crystalline solid. LC-MS: 615.26 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 1:1 mixture of rotamers δ 8.31 (s, 1 H), 8.20-8.26 (m, 1 H), 7.86 (s, 1 H), 7.70 (s, 2 H), 7.39-7.43 (m, 1 H), 6.96-7.01 (m, 1H), 6.67-6.72 (m, 1H), 5.64 (d, J=8.0 Hz, 0.5H), 5.48 (d, J=8.0 Hz, 0.5H), 4.90 (d, J=16.3 Hz, 0.5H), 4.86 (d, J=16.3 Hz, 0.5 H), 4.10-4.16 (m, 0.5 H), 3.84-3.94 (m, 1.5 H), 3.77 (s, 1.5H), 3.75 (s, 1.5H), 3.15-3.26 (m, 1H), 1.15-1.29 (m, 6 H), 0.57 (d, J=6.6 Hz, 1.5 H), 0.40 (d, J=6.6 Hz, 1.5 H).

후처리

  1. customThe resulting mixture was bubbled with nitrogen
  2. customconsumption of the starting material
  3. customThe reaction was quenched with brine
  4. extractionThe resulting mixture was extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. customThe resulting glassy mixture was purified by SiO2 (Biotage 40S cartridge, EtOAc/hexane, gradient)

출처 및 근거

ORD 기록
ord-114b106ce65d42b49c68a38a0eb70c1e
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08735435B2

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