2,6-Lutidine → HCID 178455227, compound

HRID 874823Notes

Reaction equation

HRID 874823 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.N1C(C)=CC=CC=1C.O([Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])S(C(F)(F)F)(=O)=O>C(Cl)Cl>[Si:28]([O:1][CH2:2][C@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([OH:11])=[O:10])[CH2:7][CH2:8]1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 178525728HCID 178525728, compound

Product 1

HCID 178455227HCID 178455227, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of trans-4-(1-hydroxymethyl)-cyclohexanecarboxylic acid (1.00 g, 6.32 mmol) and 2,6-lutidine (2.95 mL, 25.29 mmol) in DCM (61 mL) was added drop wise tert-butyldimethylsilyl triflate (4.36 mL, 18.96 mmol). The reaction mixture was stirred at RT for 1.5 hours. The reaction mixture was quenched with water and the organic phase removed. The aqueous phase was extracted with further DCM (×2). The combined organic extracts were combined and washed with brine, dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was dissolved in THF (30 mL) and methanol (90 mL) and 10% aqueous potassium carbonate (30 mL) added. The reaction mixture was stirred at RT for 2 hours. The solvent was evaporated at reduced pressure and the residue partitioned between water and ether. The organic phase was discarded. The aqueous phase was washed with further ether (×2). The pH of the aqueous extract was adjusted to 5 and extracted with ethyl acetate (×3). The combined ethyl acetate extracts were washed with brine, dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure to afford the title compound (1.59 g, 93%).

Workup

  1. customThe reaction mixture was quenched with water
  2. customthe organic phase removed
  3. extractionThe aqueous phase was extracted with further DCM (×2)
  4. washwashed with brine
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customthe solvent evaporated at reduced pressure
  8. dissolutionThe residue was dissolved in THF (30 mL)
  9. additionmethanol (90 mL) and 10% aqueous potassium carbonate (30 mL) added
  10. stirringThe reaction mixture was stirred at RT for 2 hours
  11. customThe solvent was evaporated at reduced pressure
  12. customthe residue partitioned between water and ether
  13. washThe aqueous phase was washed with further ether (×2)
  14. extractionThe pH of the aqueous extract
  15. extractionextracted with ethyl acetate (×3)
  16. washThe combined ethyl acetate extracts were washed with brine
  17. dry with materialdried (magnesium sulfate)
  18. filtrationfiltered
  19. customthe solvent evaporated at reduced pressure

Sources & evidence

ORD record
ord-80ccbc881b2640d993c4c62a97d15d4d
Source dataset
uspto-grants-2015_03
Patent number
US08980913B2

Reaction notes

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