KBS44-1 - Nosyl deprotection of linear amines

[KlementineJBS]

Link to HIRAC and master page #186

KBS44 Nosyl deprotection of linear amines.docx

Reaction scheme

[KlementineJBS]

27.02.24

1. Dissolved KBS49-1 (75 mg, 0.081 mmol) in dry DMF (2 mL)
2. Added thiosalicyclic acid (56.3 mg, 0.365 mmol, 4.5 equiv.) and K2CO3 (101.5 mg, 0.734 mmol, 9 equiv.)
3. heated to 60 C and left stirring from 2.35 pm

[KlementineJBS]

28.02.24

TLC from yesterday afternoon and today.

Decided to workup despite SM not being entirely consumed. RM was bright mustard yellow.

4. Diluted with LiCl solution (5%, 10 mL)
5. Added ether (40 mL)
6. washed with LiCl (3 x 20 mL) to remove DMF. These washes were bright yellow
7. Washed with Na2CO3 solution (sat., 3 x 20 mL) to deprotonate thiol acid byproduct
8. Washed with brine - solution was clear, pale yellow
9. Dried over mag sulphate and reduced.

vial: 16.0222 full: 16.0714 mass: 49.2 mg (0.0881 mmol, over 100%)

[KlementineJBS]

LRMS

Spectrum was dominated by PPh3O adducts but had evidence of desired product at 559.31 [M+H]+, as well as singly denosylated product at 745.29 [M+H]+. Minimal traces of SM were present - 720.25 [M-H]- and potentially 963.25 [M+Cl]-

KBS44-1 cr.d.zip KBS44-1 cr.pdf

[KlementineJBS]

H NMR

Peaks haven't changed greatly. Hard to interpret with such a mixture - should definitely try to purify more effectively before attempting another denosylation.

KBS44-1 cr.pdf nmr300_20240228_KBS44-1 cr_1.zip