KBS16-3 - Azidation of ferrocenylmethanol

[KlementineJBS]

Link to HIRAC, original method and master page.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Reaction Scheme

Outcome

110 mg, 40%

Notes

TLC indicated reaction completion - is low yield due to loss during purification?

[KlementineJBS]

03.05.22

KBS15 (249 mg, 1.15 mmol) was dissolved in dry THF (13 mL) and DBU (0.21 mL, 1.41 mmol, 1.2 equiv.) and DPPA (0.37 mL, 1.72 mmol, 1.5 equiv.) were added.

The reaction was heated to 60 C and left stirring from 12 pm.

TLC at 5.20 pm indicated reaction was not yet complete.

[KlementineJBS]

04.06.22

TLC at 10am indicated reaction was not yet complete. More DBU (86 μL, 0.575 mmol) and DPPA (148 μL, 0.690 mmol) was added

.

[KlementineJBS]

05.05.22

TLC at 10 am indicated reaction still wasn't complete. Added more DPPA (75 microL, 0.345 mmol, 0.3 equiv.) and DBU (52 microL, 0.345 mmol, 0.3 equiv.) at 11.30 am.

[KlementineJBS]

05.05.22

TLC at 10 am indicated reaction still wasn't complete. Added more DPPA (75 microL, 0.345 mmol, 0.3 equiv.) and DBU (52 microL, 0.345 mmol, 0.3 equiv.) at 11.30 am.

[KlementineJBS]

09.05.22

Extracted with toluene (3 X 30 mL) -- organic extract was very dark and a black colour emulsion/powder was present.

Washed with brine (60 mL) and dried over MgSO4 before rotovapping.

Vial (empty): 15.4173
Vial (product): 15.7864
Product: 315 mg (1.31 mmol, 114%)

[KlementineJBS]

11.05.22

NMR

NMR analysis was unclear. A large, broad and not well-defined peak was present at approximately 4.18, which may be the result of the 3 expected peaks merging together. In #8 (KBS16-2), a similar effect was seen prior to column purification.

KBS16-3 cr_1.zip

KBS16-3 (red) overlaid with known sample KBS16-2 (blue)

[KlementineJBS]

17.05.22

Columned crude product with hexane and ethyl acetate. Took a long time to come off with pure hexane, but overshot the mark when swapping to a gradient of 0 - 20% ethyl acetate -- next time try starting on 5% and include a small gradient up to 10% at the end?

Note fraction 3 has both product and impurity

Fractions 1 and 2 rotovapped down.