2,6-Lutidine → HCID 90357939, compound

HRID 522172Notes

Reaction equation

HRID 522172 reaction equation
[CH3:1][C:2]1([CH3:22])[O:6][C@@H:5]([C@@H:7]([OH:21])[C@@H:8]2[O:12][C:11]([CH3:14])([CH3:13])[O:10][C@@H:9]2[C@@H:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[CH2:4][O:3]1.N1C(C)=CC=CC=1C.[Si:31](OS(C(F)(F)F)(=O)=O)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].CCOC(C)=O>C(Cl)Cl.CCCCCC>[Si:31]([O:21][C@H:7]([C@H:5]1[CH2:4][O:3][C:2]([CH3:22])([CH3:1])[O:6]1)[C@@H:8]1[O:12][C:11]([CH3:13])([CH3:14])[O:10][C@@H:9]1[C@@H:15]([OH:20])[C:16]([F:18])([F:17])[F:19])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 8857Ethyl AcetateHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 90358836HCID 90358836, compound

Product 1

HCID 90357939HCID 90357939, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

In a 100 mL 2 neck round bottom flask, (R)-1-((4R,5S)-5-((R)—((R)-2,2-dimethyl-1,3-dioxolan-4-yl)(hydroxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2,2-trifluoroethanol (1 g, 3.03 mmol) and 2,6-lutidine (1 g, 9.09 mmol, commercially available from Sigma Aldrich, India) was taken up in dry DCM (50 mL) at 0° C. under a nitrogen atmosphere. TBSOTf (2.4 g, 9.09 mmol, commercially available from Sigma Aldrich, India) was added to the above reaction mixture at the same temperature under a nitrogen atmosphere. The reaction mixture was stirred for 30 min at 0° C. and then the temperature was slowly raised to rt and the mixture stirred at rt for 3 h. Upon completion of the reaction (TLC, 20% EtOAc in hexane Rf 0.5), the reaction mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), and were then concentrated under reduced pressure. The residue obtained was purified by silica gel (60-120 mesh) column chromatography (gradient elution 10-15% EtOAc-hexanes) to give (R)-1-((4R,5R)-5-((R)-((tert-butyldimethylsilyl)oxy)((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2,2-trifluoroethanol as a pale yellow oil (0.7 g, 50%): 1H NMR (400 MHz, CDCl3) δ 4.52-4.45 (m, 2H), 4.29-4.25 (m, 1H), 4.22-4.19 (m, 1H), 4.04-3.93 (m, 2H), 3.78-3.74 (t, J=8.0 Hz, 1H), 2.70 (d, J=11.2 Hz, 1H), 1.55 (s, 3H), 1.40 (d, J=9.6 Hz, 3H), 0.86 (s, 9H), 0.11 (d, J=3.2 Hz, 6H), 5 H were obscured.

Workup

  1. temperaturethe temperature was slowly raised to rt
  2. stirringthe mixture stirred at rt for 3 h
  3. customthe reaction mixture was quenched with saturated NaHCO3 solution
  4. extractionextracted with EtOAc (3×20 mL)
  5. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  6. concentrationwere then concentrated under reduced pressure
  7. customThe residue obtained
  8. customwas purified by silica gel (60-120 mesh) column chromatography (gradient elution 10-15% EtOAc-hexanes)

Sources & evidence

ORD record
ord-fcad7fb79d044146907465ce2a102c76
Source dataset
uspto-grants-2016_05
Patent number
US09328134B2

Reaction notes

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