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

HRID 451757Notes

Reaction equation

HRID 451757 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-6f720384f4044f04908554e8938e63ca
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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