m-Chloroperbenzoic acid → (S)-tert-butyl 4-((1-fluorocyclohexyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 451757ノート

反応式

HRID 451757 の反応式
O[C:2]1([CH2:8][C@H:9]2[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[N:10]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.CCN(S(F)(F)[F:29])CC.C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[F:29][C:2]1([CH2:8][C@H:9]2[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[N:10]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

参加物

5

反応物 3

HCID 70297m-Chloroperbenzoic acidHCID 123472(Diethylamino)sulfur trifluorideHCID 59201544(S)-tert-Butyl 4-((1-hydroxycyclohexyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate

生成物 1

HCID 59201498(S)-tert-butyl 4-((1-fluorocyclohexyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate収率 26.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

(S)-tert-Butyl 4-((1-hydroxycyclohexyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (2.70 g, 8.63 mmol) was dissolved in CH2Cl2 and the solution was cooled to −78° C. DAST (2.78 g, 17.2 mmol, 2.0 equiv) was added via syringe and the solution was stirred overnight with concomitant warming to rt. LC-MS showed consumption of the starting alcohol. Satd aq NaHCO3 was added and the mixture was stirred for 1 h. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, and filtered. The resulting solution was treated with m-CPBA (1.5 g, 8.6 mmol) and stirred for 3 h. After this time the olefinic by-products from the fluorination were consumed. The excess m-CPBA was quenched by addition of 10% aq Na2S2O3 (50 mL). The layers were separated and the organic layer was washed with satd aq NaHCO3 and brine, dried over Na2SO4, filtered and evaporated. Flash chromatography on silica, eluting with 0-29% EtOAc in hexanes, afforded (S)-tert-butyl 4-((1-fluorocyclohexyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (725 mg).

後処理

  1. temperaturewith concomitant warming to rt
  2. customconsumption of the starting alcohol
  3. additionSatd aq NaHCO3 was added
  4. stirringthe mixture was stirred for 1 h
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. stirringstirred for 3 h
  10. customAfter this time the olefinic by-products from the fluorination were consumed
  11. customThe excess m-CPBA was quenched by addition of 10% aq Na2S2O3 (50 mL)
  12. customThe layers were separated
  13. washthe organic layer was washed with satd aq NaHCO3 and brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. customevaporated
  17. washFlash chromatography on silica, eluting with 0-29% EtOAc in hexanes

出典と根拠

ORDレコード
ord-6f720384f4044f04908554e8938e63ca
出典データセット
uspto-grants-2013_07
特許番号
US08487108B2

反応ノート

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