Sodium bis(trimethylsilyl)amide → methyl 2''-{[(4S,5R)-5-(3-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 607119노트

반응식

HRID 607119 반응식
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[O:12][C:11](=[O:13])[NH:10][C@H:9]2[CH3:14])[CH:5]=[CH:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:26][C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=1[C:37]1[CH:38]=[C:39]([C:45]2[CH:50]=[CH:49][C:48]([C:51]([O:53][CH3:54])=[O:52])=[CH:47][C:46]=2[CH3:55])[CH:40]=[CH:41][C:42]=1[O:43][CH3:44]>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[O:12][C:11](=[O:13])[N:10]([CH2:26][C:27]3[CH:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:30]=[CH:29][C:28]=3[C:37]3[CH:38]=[C:39]([C:45]4[CH:50]=[CH:49][C:48]([C:51]([O:53][CH3:54])=[O:52])=[CH:47][C:46]=4[CH3:55])[CH:40]=[CH:41][C:42]=3[O:43][CH3:44])[C@H:9]2[CH3:14])[CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylateHCID 67066030(4S,5R)-5-(3-fluorophenyl)-4-methyl-1,3-oxazolidin-2-one

생성물 1

HCID 25009328methyl 2''-{[(4S,5R)-5-(3-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매2회

실험 절차

To a 0° C. solution of (4S,5R)-5-(3-fluorophenyl)-4-methyl-1,3-oxazolidin-2-one (16.2 mg, 0.0830 mmol) in DMA (1 mL) was added NaHMDS (83 μL, 0.083 mmol). Next, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (49 mg, 0.0996 mmol) in DMA (1 mL) was added via cannula. After 5 minutes, the reaction was quenched with saturated NH4Cl solution (10 mL) and diluted with EtOAc (20 ml). The aqueous layer was extracted with EtOAc (20 mL), and the combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes) afforded methyl 2″-{[(4S,5R)-5-(3-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS=608.2 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) a 7.94 (d, J=5.9 Hz, 1H), 7.87 (d, J=7.8 Hz, 1H), 7.71-7.61 (m, 2H), 7.41-7.36 (m, 2H), 7.33-7.24 (m, 2H), 7.14-7.12 (m, 1H), 7.07-7.05 (m, 1H), 7.02-6.90 (m, 3H), 5.46 (d, J=8.2 Hz), 5.24 (d, J=8.2 Hz), 4.90 (d, J=15.8 Hz), 4.82 (d, J=15.8 Hz), 4.20 (d, J=15.8 Hz), 3.97 (d, J=15.8 Hz), 3.92 (s, 3H), 3.95 (s, 3H), 3.75-3.69 (m, 1H), 2.36 (s), 2.31 (s), 0.53 (d, J=6.6 Hz), 0.43 (d, J=6.6 Hz).

후처리

  1. customthe reaction was quenched with saturated NH4Cl solution (10 mL)
  2. additiondiluted with EtOAc (20 ml)
  3. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  4. washthe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-add8449591f54649a1bdfcf144d6dd1c
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915271B2

반응 노트

불러오는 중…