KBS17-8 - Propargylation of 1,6-diaminohexane

[KlementineJBS]

Link to HIRAC, original method and master page.

Last attempt is #32. Next attempt is #45.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Using DMF as solvent. Add NaH portionwise (and use only 3 equiv.), allow 1-2 hrs reaction time and cool reaction to 0 C before adding propargyl bromide.

Outcome

[KlementineJBS]

20.09.22

1. Added NaH (105 mg, 2.63 mmol, 1.89 equiv.) to a flask under nitrogen
2. Added KBS3-3 (1.39 mmol) via solution transfer (15 mL dry THF, 1 mL dry DMF)
3. Left stirring from 4.40 pm
4. Added propargyl bromide (0.4 mL, 80% in toluene, 4.26 mmol, 3.1 equiv.) at 6.10 pm ON ICE
5. Left stirring in ice bath

[KlementineJBS]

21.09.22

Removed ice bath (by now a water bath) and TLC'd.

TLC indicated that bis product was forming slowly. Left to keep reacting.

[KlementineJBS]

23.09.22

TLC not much different to Wednesday. Added 0.25 mL propargyl bromide and left stirring.

[KlementineJBS]

26.09.22

TLC indicated completion at 10 am, added 50 mL NH4Cl solution to quench and left stirring until 3pm.

Then:

• extracted with toluene (3 x 50 mL)
• washed with water to remove DMF (5 x 100 mL)
• washed with brine (100 mL)
• dried over MgSO4

Crude product

Empty vial: 16.1950 Full vial: 16.6136 Mass: 418.6 mg

H NMR

KBS17-8 cr_1.zip KBS17-8 cr processed.pdf

Again, appears to have both mono and bis products present.

[KlementineJBS]

LRMS

B

KBS17-8 B.pdf KBS17-8 B.d.zip

D

KBS17-8 D.pdf KBS17-8 D.d.zip

[KlementineJBS]

Column details

Manual column run on ~11 cm silica with ethyl acetate/petroleum benzine.

5% - 150 mL 10% - 300 mL 50% - 100 mL 100% - 100 mL