KBS43-3 - Nosyl protection of 1,6-diaminohexane

[KlementineJBS]

Link to HIRAC and master page.

KBS43 - Nosyl protection of linear diamine .docx

Rationale

Nosyl is an electron deficient PG and will help to stabilise the N- required during the alkylation reaction. Alternatiavely, a nosyl-protected amine could participate in the Fukuyama-Mitsunobu reaction.

Reaction scheme

Outcome

5.313 g (10.9 mmol, 64%)

[KlementineJBS]

1. Added linear amine SM (1.9849 g, 17.1 mmol) to a flask with 40 mL DCM
2. Added NEt3 (7.2 mL, 51.3 mmol, 3 equiv.)
3. Cooled to 0 C
4. Added nosyl chloride portionwise (9.0285 g, 40.9 mmol, 2.4 equiv.)
5. Added 40 mL extra DCM
6. Left stirring from 12

TLC indicated some reaction at 12.45 pm but consumption of starting material was hard to determine. Added 70 mL more DCM.

[KlementineJBS]

Worked up despite multiple spots - a second TLC with ninhydrin revealed little to no SM remaining.

7. quenched with ammonium chloride (80 mL)
8. extracted with chloroform (3 x 80 mL)
9. washed with brine
10. Dried poorly over mag sulphate and filtered using a sintered funnel. a large amount of powdery white solid was collected, as well as a yellow filtrate which was rotovapped down to give a dark green liquid.

[KlementineJBS]

After NMRing both filtrate and solid, it was determined that solid was the desired product. This was washed with water to remove mag sulphate and vacuum filtered again, then dried under hi vac.

In future, should try to collect precipitate rather than do a liquid-liquid workup.

[KlementineJBS]

H NMR

Peaks look good. Some water in sample.

KBS43-3 cr DMSO_1 (1).zip KBS43-3 crude.pdf