Oxolane--water (1/1) → (S)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 406665

反応式

HRID 406665 の反応式
[CH2:1]([C@@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=C.C1C[O:37]CC1.O>CCOC(C)=O.O=[Os](=O)(=O)=O>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C@:4]2([CH2:1][CH2:2][OH:37])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]3[CH:14]=[CH:15][C:16]([C:19]4[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=4)=[CH:17][CH:18]=3)[CH3:12])[CH2:6][CH2:5]2)=[CH:28][CH:29]=1

参加物

5

反応物 2

HCID 21881883Oxolane--water (1/1)HCID 59635724(R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

生成物 1

HCID 59635715(S)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

試薬・触媒・溶媒 2

HCID 30318Osmium Tetroxide触媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (0.064 g, 0.144 mmol, 1.0 equiv) in THF-H2O (1:1, 6 mL) were added NalO4 (0.145 g, 0.678 mmol, 4.7 equiv) and OsO4 (2.5 wt. % solution in t-BuOH, 0.048 g, 0.0047 mmol, 0.033 equiv), and the mixture was stirred at rt for 1 h. The mixture was diluted with EtOAc, dried over Na2SO4, and concentrated under reduced pressure. The residue was dissolved in MeOH (3 mL) and NaBH4 (0.100 g) was added. After the mixture was stirred for 0.5 h at rt, acetone was added. The solvents were removed in vacuo, the residue was treated with saturated brine, extracted with CH2Cl2, and dried over Na2SO4. After the solvent was evaporated, the residue was purified by reversed-phase HPLC (SunFire™ Prep O18 OBD™ 5 μm 19×50 mm column, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 2 min, flow rate 20 mL/min) to afford (S)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one. LC-MS Method 1 tR=1.21 min, m/Z=451 (M+1); 1H NMR (400 MHz, CD3OD) δ 7.80 (m, 1H), 7.69 (d, J=9.4 Hz, 1H), 7.22-7.19 (m, 4H), 7.00-6.92 (m, 4H), 6.52 (d, J=9.4 Hz, 1H), 5.45 (q, J=7.0 Hz, 1H), 3.60-3.52 (m, 1H), 3.52 (s, 3H), 3.24-3.18 (m, 1H), 3.02-2.98 (m, 1H), 2.39-2.35 (m, 1H), 2.23-2.12 (m, 2H), 2.01 (t, J=7.3 Hz, 2H), 1.43 (d, J=7.0 Hz, 3H); 19F NMR (376 MHz, CD3OD) 8-117.19 (m).

後処理

  1. dry with materialdried over Na2SO4
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in MeOH (3 mL)
  4. additionNaBH4 (0.100 g) was added
  5. additionacetone was added
  6. customThe solvents were removed in vacuo
  7. additionthe residue was treated with saturated brine
  8. extractionextracted with CH2Cl2
  9. dry with materialdried over Na2SO4
  10. customAfter the solvent was evaporated
  11. customthe residue was purified by reversed-phase HPLC (SunFire™ Prep O18 OBD™ 5 μm 19×50 mm column, 10%
  12. customover 8 min
  13. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

出典と根拠

ORDレコード
ord-84d8ab2dff6b4804a5ca84a82c9d65d4
出典データセット
uspto-grants-2014_06
特許番号
US08754076B2

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