Tetrahydrofuran → tert-Butyl 3-(fluoro(phenylsulfonyl)methylene)azetidine-1-carboxylate

HRID 1692983ノート

反応式

HRID 1692983 の反応式
[C:1]1([S:7]([CH2:10][F:11])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(=O)(OCC)OCC.O1CCCC1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].O=[C:37]1[CH2:40][N:39]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38]1.[Cl-].[NH4+]>CCOC(C)=O>[F:11][C:10](=[C:37]1[CH2:38][N:39]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:40]1)[S:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)(=[O:9])=[O:8]

参加物

8

反応物 6

HCID 8028Tetrahydrofuran3 回HCID 13139Diethyl chlorophosphateHCID 25517Ammonium ChlorideHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 2733832Lithium HexamethyldisilazideHCID 2759036Fluoromethyl Phenyl Sulfone

生成物 1

HCID 66824343tert-Butyl 3-(fluoro(phenylsulfonyl)methylene)azetidine-1-carboxylate収率 77.5%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

To a mixture of fluoromethyl phenyl sulfone (0.50 g, 2.9 mmol) and phosphorochloridic acid, diethyl ester (0.415 mL, 2.87 mmol) in tetrahydrofuran (6 mL, 70 mmol) was added 1.000 M of lithium hexamethyldisilazide in tetrahydrofuran (6.2 mL, 6.2 mmol) dropwise at −78° C. After the mixture was stirred at −78° C. for 1 h, a solution of tert-butyl 3-oxoazetidine-1-carboxylate (0.378 g, 2.21 mmol) in tetrahydrofuran (1.3 mL, 16 mmol) was added. The reaction was allowed to warm to ambient temperature and stirred for 2 h at rt. The reaction was poured into an ice-cold mixture of EtOAc and sat. ammonium chloride. The organic layer was separated and the aq. layer was extracted with EtOAc. The combined organic layers were washed with brine, and dried over sodium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified on silica gel, eluting with 0 to 50% EtOAc in hexane, to give the desired product (560 mg, 77.5%). LCMS calculated for C15H18FNO4SNa(M+Na)+: m/z=350.1; Found (M+Na) 350.3.

後処理

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 2 h at rt
  3. customThe organic layer was separated
  4. extractionthe aq. layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe resulting residue was purified on silica gel
  9. washeluting with 0 to 50% EtOAc in hexane

出典と根拠

ORDレコード
ord-81bfd705a94940f69dfa4bda64892a4c
出典データセット
uspto-grants-2012_04
特許番号
US08158616B2

反応ノート

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