Triethylamine → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(4-fluoro-5-isopropyl-2-methoxyphenyl)-3-methylisoxazol-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 604655

反応式

HRID 604655 の反応式
C(N(CC)CC)C.[F:8][C:9]([F:43])([F:42])[C:10]1[CH:11]=[C:12]([C@H:20]2[O:24][C:23](=[O:25])[N:22]([CH2:26][C:27]#[C:28][C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[C@H:21]2[CH3:41])[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1.[OH:44][N:45]=[C:46](Cl)[CH3:47]>C1(C)C=CC=CC=1.Cl>[F:43][C:9]([F:8])([F:42])[C:10]1[CH:11]=[C:12]([C@H:20]2[O:24][C:23](=[O:25])[N:22]([CH2:26][C:27]3[C:46]([CH3:47])=[N:45][O:44][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[C@H:21]2[CH3:41])[CH:13]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:15]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 69633Ethanimidoyl chloride, N-hydroxy-HCID 86627633(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one

生成物 1

HCID 24969897(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(4-fluoro-5-isopropyl-2-methoxyphenyl)-3-methylisoxazol-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 1140Toluene溶媒

実験手順

Triethylamine (123.4 mg, 170 μL, 1.21 mmol) was added to a stirred solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one (21.9 mg, 0.0423 mmol) and N-hydroxyethanimidoyl chloride (124.4 mg, 1.33 mmol) in dry toluene (2 mL) at room temperature under N2. The reaction was heated at reflux for 2 days. The reaction mixture was cooled to room temperature, diluted with 1N HCl and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(4-fluoro-5-isopropyl-2-methoxyphenyl)-3-methylisoxazol-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.38 (20% EtOAc/hexanes). LCMS calc.=575.2; found=575.3 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 7.84 (s, 1H); 7.64 (s, 2H); 7.31 (d, J=8.3 Hz, 1H); 6.68 (d, J=11.8 Hz, 1H); 5.27 (d, J=8.0 Hz, 1H); 4.78 (d, J=15.6 Hz, 1H); 4.00 (d, J=15.6 Hz, 1H); 3.82 (s, 3H); 3.72-3.68 (m, 1H); 3.22-3.16 (m, 1H); 2.38 (s, 3H); 1.24 (d, J=7.0 Hz, 3H); 1.22 (d, J=7.0 Hz, 3H); 0.42 (d, J=6.6 Hz, 3H).

後処理

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 2 days
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient)

出典と根拠

ORDレコード
ord-de6bc5cab68248e9b91e7872992d59d2
出典データセット
uspto-grants-2011_03
特許番号
US07910592B2

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