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

HRID 2093224노트

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HRID 2093224 반응식
C([O:8][C:9](=[O:23])[NH:10][C@@H:11]([CH3:22])[C@H:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:35][C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][C:37]=1[C:46]1[CH:47]=[C:48]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:56][C:55]=2[CH3:64])[CH:49]=[CH:50][C:51]=1[O:52][CH3:53]>CC(N(C)C)=O.C1COCC1>[CH3:53][O:52][C:51]1[CH:50]=[CH:49][C:48]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:56][C:55]=2[CH3:64])=[CH:47][C:46]=1[C:37]1[CH:38]=[CH:39][C:40]([C:42]([F:45])([F:43])[F:44])=[CH:41][C:36]=1[CH2:35][N:10]1[C@@H:11]([CH3:22])[C@@H:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[O:23][C:9]1=[O:8]

참가 물질

6

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylateHCID 86630550benzyl[(1S,2R)-2-hydroxy-2-(3-methoxyphenyl)-1-methylethyl]carbamate

생성물 1

HCID 25009504methyl 4'-methoxy-2''-{[(4S,5R)-5-(3-methoxyphenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 31374Dimethylacetamide용매2회

실험 절차

To a 0° C. solution of benzyl[(1S,2R)-2-hydroxy-2-(3-methoxyphenyl)-1-methylethyl]carbamate (40 mg, 0.126 mmol) in DMA (1.5 mL) was added NaHMDS (0.246 mL of a 1M solution in THF, 0.246 mmol). After 5 minutes, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (68 mg, 0.138 mmol) in DMA (2.5 mL) was added via cannula. After 5 minutes, the reaction was quenched with saturated NH4Cl solution (10 mL), diluted with EtOAc (20 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 25% acetone/hexanes), followed by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) afforded methyl 4′-methoxy-2″-{[(4S ,5R)-5-(3-methoxyphenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS=644.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.94-7.86 (m, 2H), 7.71-7.62 (m, 2H), 7.43-7.36 (m, 2H), 7.31-7.22 (m, 2H), 7.3 (m, 1H), 7.08-7.05 (m, 1H), 6.85-6.83 (m, 1H), 6.75-6.68 (m, 2H), 5.45 (d, J=8.0 Hz), 5.23 (d, J=8.0 Hz), 4.89 (d, J=16.0 Hz), 4.82 (d, J=16.0 Hz), 4.20 (d, J=15.8 Hz), 3.96 (d, J=15.8 Hz), 3.91 (s, 3H), 3.85 (s, 3H), 3.77-3.75 (m, 3H), 3.72-3.69 (m, 1H), 2.31 (s), 2.08 (s), 0.54 (d, J=6.4 Hz), 0.44 (d, J=6.4 Hz).

후처리

  1. waitAfter 5 minutes
  2. customthe reaction was quenched with saturated NH4Cl solution (10 mL)
  3. additiondiluted with EtOAc (20 mL)
  4. washwashed 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 (0 to 25% acetone/hexanes)

출처 및 근거

ORD 기록
ord-5a1c98ac5c3c4b6a849585c420b1268f
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440702B2

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