Tetrabutylammonium Fluoride → (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one

HRID 1186183ノート

反応式

HRID 1186183 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:34])=[C:6]([C@:8]([N:19]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:20](=[O:24])[CH2:21][CH2:22]Cl)([CH3:18])[CH2:9][O:10][Si](C(C)(C)C)(C)C)[CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:34])=[C:6]([C@@:8]2([CH3:18])[N:19]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[C:20](=[O:24])[CH2:21][CH2:22][O:10][CH2:9]2)[CH:7]=1

参加物

4

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 58562947N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide

生成物 1

HCID 58563118(R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

N-[(R)-1-(5-Bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide (2.08 g, 3.63 mmol) was dissolved in tetrahydrofurane (45 ml) and the solution cooled to 0° C. A solution of tetrabutylammonium fluoride (1 N in tetrahydrofuran, 7.25 ml) was added and the reaction mixture left to warm to room temperature. After 16 hours, the solvent was evaporated at reduced pressure, the residue dissolved in ethyl acetate (25 ml) and water (25 ml) and the mixture stirred for 15 minutes at room temperature. The aqueous layer was separated and extracted with ethyl acetate (50 ml). The organic layers were washed with brine (25 ml), combined, dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 20/10 as the eluent, (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one (intermediate C10A) was obtained as a white foam (1.34 g, 88% of theory). MS (ISP): m/z=422.1, 424.2 [M+H]+.

後処理

  1. waitthe reaction mixture left
  2. temperatureto warm to room temperature
  3. customthe solvent was evaporated at reduced pressure
  4. dissolutionthe residue dissolved in ethyl acetate (25 ml)
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate (50 ml)
  7. washThe organic layers were washed with brine (25 ml)
  8. dry with materialdried over sodium sulfate
  9. customevaporated at reduced pressure

出典と根拠

ORDレコード
ord-399e0a9246d345678dbb9ccc97c79310
出典データセット
uspto-grants-2014_03
特許番号
US08673894B2

反応ノート

読み込み中…