4-Phenylpyridine-1-oxide → N-((R)-1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3,3-bis(trifluoromethyl)oxirane-2-carboxamide

HRID 238799

反応式

HRID 238799 の反応式
[F:1][C:2]([F:46])([F:45])[C:3]([C:41]([F:44])([F:43])[F:42])=[CH:4][C:5]([NH:7][C@:8]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH:38]([CH3:40])[CH3:39])[CH:31]=1)([C:16]1[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6].C1(C2C=C[N+]([O-:59])=CC=2)C=CC=CC=1.[O-]Cl.[Na+]>C(#N)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C@@:8]([NH:7][C:5]([CH:4]2[C:3]([C:41]([F:43])([F:44])[F:42])([C:2]([F:1])([F:45])[F:46])[O:59]2)=[O:6])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:31][C:32]=1[O:37][CH:38]([CH3:40])[CH3:39]

参加物

5

反応物 3

HCID 708034-Phenylpyridine-1-oxideHCID 23582231HCID 23582231、化合物HCID 23665760Sodium Hypochlorite

生成物 1

HCID 86613054N-((R)-1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3,3-bis(trifluoromethyl)oxirane-2-carboxamide収率 74%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
0 °C

実験手順

At 0° C. to a solution of (R)-4,4,4-trifluoro-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)but-2-enamide (Example 291, 130 mg, 0.19 mmol) and 4-phenyl pyridine N-oxide (26 mg, 0.15 mmol) in acetonitrile (5 mL) was added NaOCl solution (206 μL, chlorine wt % 10-3%, 0.58 mmol). The reaction mixture was stirred at 0° C. for 10 min, then at rt for 1 h. The solvents were removed under reduced pressure and the residue was diluted with EtOAc (30 mL), washed with saturated Na2SO3 (30 mL), dried over MgSO4, filtered and concentrated. The resulting residue was right away purified by ISCO chromatography (40 g column, flow rate 25 mL/min) using hexanes/EtOAc (0-10% over 30 min) to give N—((R)-1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3,3-bis(trifluoromethyl)oxirane-2-carboxamide as a diastereomer mixture at a retention time of 26 min (97 mg, 74% yield). The diastereomer mixture was separated by Chiral preparative HPLC chiralpak AD 20μ column, 5×50 cm, eluting with 5% IPA/Heptane with flow rate 50 mL/min.

後処理

  1. waitat rt for 1 h
  2. customThe solvents were removed under reduced pressure
  3. additionthe residue was diluted with EtOAc (30 mL)
  4. washwashed with saturated Na2SO3 (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was right away purified by ISCO chromatography (40 g column, flow rate 25 mL/min)
  9. customhexanes/EtOAc (0-10% over 30 min)

出典と根拠

ORDレコード
ord-67715dc56fc5493f970b6f8ac4158070
出典データセット
uspto-grants-2014_02
特許番号
US08642576B2

関連ノート

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