Hydrochloric Acid → (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxy-propyl)-1,3-oxazinan-2-one

HRID 450988ノート

反応式

HRID 450988 の反応式
[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:31]CC1.[OH-].[Na+].OO.Cl>C1COCC1.O>[Br:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C@@:4]([C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)([CH2:1][CH2:2][CH2:3][OH:31])[O:9][C:8]2=[O:10])[CH3:12])=[CH:14][CH:15]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 53473487(R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one

生成物 1

HCID 59532370(R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxy-propyl)-1,3-oxazinan-2-one収率 38%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (1 g, 2.4 mmol) in dry THF (15 mL) was added dropwise BH3.THF (5 mL, 1 M) at 0° C. After stirring for 2 h at rt, the reaction mixture was cooled to 0° C. and water (1 mL), aqueous NaOH (0.5 mL, 3 M) and H2O2 (0.5 mL, 30%) were successively added. The mixture was stirred for 2-3 h at rt and diluted with water (8 mL). The pH was adjusted to 6-7 with 0.5 N HCl. The layers were separated, and the aqueous phase was extracted with EtOAc (3×10 mL). The combined organic layers were washed with a satd aq NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified by preparative TLC to afford (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (400 mg, 38%).

後処理

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. stirringThe mixture was stirred for 2-3 h at rt
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
  5. washThe combined organic layers were washed with a satd aq NaHCO3 (20 mL) and brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give the crude product, which
  9. customwas purified by preparative TLC

出典と根拠

ORDレコード
ord-777d15558a884a608f6e33241bcbaa67
出典データセット
uspto-grants-2013_07
特許番号
US08487094B2

反応ノート

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