Trifluoroacetic acid → (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-hydroxybenzyl)morpholine

HRID 369824

反応式

HRID 369824 の反応式
[O:1]=[C:2]1[C@H:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][Si](C(C)(C)C)(C)C)=[C:11]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:10]=2)[N:6](C(OC(C)(C)C)=O)[C@@H:5]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:4]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[O:3]1.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-].C1COCC1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(Cl)Cl.CCCCCC.C1COCC1>[O:1]=[C:2]1[C@H:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([C:23]([CH3:26])([CH3:24])[CH3:25])[CH:10]=2)[NH:6][C@@H:5]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C@@H:4]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[O:3]1

参加物

9

反応物 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 11078149TBAF tetrahydrofuranHCID 57296200tert-butyl (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-((tert-butyldimethylsilyl)oxy)benzyl)-4-morpholinecarboxylate

生成物 1

HCID 57303814(2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-hydroxybenzyl)morpholine収率 89.4%

試薬・触媒・溶媒 4

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒2 回HCID 8857Ethyl Acetate溶媒3 回

実験手順

To a 250 mL 3-necked flask equipped with a nitrogen inlet and a magnetic stirrer were added 4.51 g of tert-butyl (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-((tert-butyldimethylsilyl)oxy)benzyl)-4-morpholinecarboxylate and 50 mL of anhydrous THF. The solution was cooled in an ice water bath, treated with 7.51 mL of 1M nBu4NF/THF (Aldrich), and then allowed to warm to RT with stirring under nitrogen. After 1.5 h, tlc (SiO2, 85:15 hexane:EtOAc) indicated no remaining starting material and a single new component at Rf =0.52. The solution was diluted with 125 mL of EtOAc, washed with water (4×100 mL), dried over MgSO4, and concentrated to give a thick, clear oil. Mass spectral analysis (APCI) indicated the desired intermediate with m/e=538 (M+H+Na)+. The oil was dissolved in 50 mL of CH2Cl2 and the solution treated with 15 mL of TFA. After stirring for 40 min, tlc (SiO2, 65:35 hexane:EtOAc) indicated a single new component at Rf =0.36. The solution was neutralized by addition of saturated aqueous NaHCO3. The mixture was transferred to a separatory funnel and the layers separated. The CH2Cl2 solution was washed with additional saturated NaHCO3 (3×50 mL), dried over MgSO4 and concentrated in vacuo to give a clear foam. The crude product was purified by flash chromatography (SiO2, 7:3 hexane:EtOAc) to afford 2.66 g (89%) of (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-tert-butyl-4-hydroxybenzyl)morpholine as a white foam, m.p. 76-80° C.

後処理

  1. customTo a 250 mL 3-necked flask equipped with a nitrogen inlet and a magnetic stirrer
  2. temperatureThe solution was cooled in an ice water bath
  3. washwashed with water (4×100 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give a thick, clear oil
  7. stirringAfter stirring for 40 min
  8. customThe mixture was transferred to a separatory funnel
  9. customthe layers separated
  10. washThe CH2Cl2 solution was washed with additional saturated NaHCO3 (3×50 mL)
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customto give a clear foam
  14. customThe crude product was purified by flash chromatography (SiO2, 7:3 hexane:EtOAc)

出典と根拠

ORDレコード
ord-dbdef79da0374f10958d5837cd84d721
出典データセット
uspto-grants-2000_10
特許番号
US06140100

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