KBS17-6 - Propargylation of 1,6-diaminohexane

[KlementineJBS]

Link to HIRAC, original method and master page.

Last attempts are #19 and #23.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

[KlementineJBS]

09.08.22

1. Dissolved KBS3 (1.00 g, 3.17 mmol) in dry DMF (20 mL)
2. Added NaH (1.748 g, 26.9 mmol, 8.5 equiv.)
3. Added propargyl bromide (1.00 mL, 10.6 equiv.)

Reaction immediately went a dirty brown dishwater colour.

Within a few minutes, reaction was completely black.

[KlementineJBS]

10.08.22

TLC at 11 am indicated reaction was complete.

4. Quenched with NH4Cl (40 mL). Make sure to do this DROPWISE
5. Diluted with water (60 mL)
6. Extracted with toluene (3 x 125 mL)
7. Washed with water (5 x 200 mL)

[KlementineJBS]

11.08.22

Empty vial: 16.0985
Full vial: 17.2010
Mass: 1.1025 g

[KlementineJBS]

12.08.22

Second extraction

Empty vial: 15.8755
Full vial: 16.4060
Mass: 530.5 mg

[KlementineJBS]

15.08.22

LRMS

For both:

KBS17-6 cr.pdf
KBS17-6 cr.d.zip

KBS17-6 cr 2nd extract.pdf
KBS17-6 cr 2nd extract.d.zip

[KlementineJBS]

25.08.22

Fractions	Empty vial	Full vial	Mass (mg)	Moles	%	Species
1-12	15.8657	15.8807	15	0.038	-	-
13-18	16.2209	16.2943	73.4	0.187	-	-
19-27	15.9732	15.9892	16	0.041	-	-
28-47	16.0098	16.0273	17.5	0.045	-	-
Column runoff	16.1856	16.1994	13.8	0.035	-	-

NMR

KBS17-6 column (2nd extract).zip
KBS17-6 column (2nd extract).pdf

None of these seem to have any product. Will try flushing column with 100% ethyl acetate.

[KlementineJBS]

26.08.22

Flushed with 100% ethyl acetate (2nd flush, 30-100 over 3 CV, 100 for 9 CV). NMR unclear, but mass spec indicates only SM present (339 is [M+Na]).

KBS17-6 2nd flush.zip
KBS17-6 2nd flush processed.pdf

Mass spec

KBS17-6 2nd flush.pdf
KBS17-6 2nd flush.d.zip

[KlementineJBS]

01.09.22

Manual column

~ 15 cm silica

Starting with 200 mL of 5:95 EtOac:hexanes
100 mL 10:90 as above
100 mL 50:50
150 mL straight ethyl acetate
100 mL 10:90 MeOH:DCM

Fractions	Action	Empty vial	Full vial	Mass (mg)	Moles	% Yield
3-15	Mono and bis product	16.0363	16.6931	656.8	1.67	53
16-19	Unknown	15.9959	15.9993	3.4	0.0087	0.3
20-28	Unknown	16.0607	16.0638	3.1	0.0079	0.2
29 onwards	SM	15.8642	15.9108	46.9	0.119	4

Vial after loading sample: 16.1523