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KlementineJBS / USYD_PhD_ELN

This repository forms the electronic laboratory notebook (ELN)for Klementine Burrell-Sander's PhD's
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KBS52-1 - Nosyl deprotection of KBS51 #191

Closed KlementineJBS closed 2 months ago

KlementineJBS commented 3 months ago

Link to HIRAC and master page #186

Reaction scheme

image

KlementineJBS commented 2 months ago

17.04.24

Followed protocol in #190

Amounts: KBS51 - 120.5 mg, 0.109 mmol thiol (2,2′-(Ethylenedioxy)diethanethiol) - 71 uL potassium carbonate - 121 mg

Initially left stirring at room temp for ~24 hours,

KlementineJBS commented 2 months ago

18.04.24

Heated to 60 C from ~9 am. Then heated to 80 C from 11.30 am.

Took a crude NMR in the afternoon that indicated little formation of deprotected product.

KlementineJBS commented 2 months ago

19.04.24

Still not seeing consumption of SM but wanted to work up anyway.

  1. Diluted with ether (25 mL)
  2. Washed with LiCl solution (5%, 3 x 25 mL)
  3. Washed with Na2CO3 solution (sat., 25 mL)
  4. Washed with brine and dried over mag sulphate

vial: mass:

Decided to carry out a second extraction with DCM on the combined LiCl washes. Used 3 x 25 mL DCM, washed combined organic extracts again with LiCl and dried over mag sulphate.

vial: mass:

KlementineJBS commented 2 months ago

H NMR

Unfortunately integrals suggest very little conversion - 12:1 ratio of SM:product going off integrals for methylene peak at 4.77/4.00. Both extracts seem very similar - maybe should try using DCM in future workups

KBS52-1 cr.pdf

nmr300_20240419_KBS52-1 2nd extract_1.zip nmr300_20240418_KBS52-1 RM_1.zip nmr300_20240419_KBS52-1 1st extract_1.zip

KlementineJBS commented 2 months ago

LRMS

Interestingly different peaks were seen for the two extracts.

First extract 434.16+, 447.03+, 463.11+, 663.22+, 845.26(3+)

Second extract 545.35+ [M+H]+ of product 916+ [M+H]+ and 938.35 [M+Na]+ of singly deprotected amine 990.23- 517.29+ 589.43+ 633.42+

KBS52-1 extracts.d.zip KBS52-1 2nd extract.pdf KBS52-1 1st extract.pdf

KlementineJBS commented 2 months ago

22.04.24

Quick silica plug to remove leftover thiol and thiol byproduct.

Washed with 100 mL of 65% EtOAc in hexanes, 100 mL 80%, 100 mL 100% and then 100 mL 10% MeOH in DCM (with NH4) and 50 mL straight methanol w NH4OH.

Gratifyingly, the methanol collections appear to contain only amine and the thiol is cleanly in the ethyl acetate collections.

KlementineJBS commented 2 months ago

H NMR

Should use both "mix" and "plug" as both contain product (shown by NMR).

nmr300_20240423_KBS52-1 plug mix_1.zip nmr300_20240423_KBS52-1 plug_1.zip KBS52-1 silica plug.pdf