KBS28-7 - Click coupling of 1-azido-naphthyl and propargyl alcohol

[KlementineJBS]

Link to HIRAC and master page. Original method can be found in J. Batten's PhD thesis (2022).

KBS28 - Click coupling with 1-azidonaphthalene and propargyl alcohol.docx

Previous attempt is #151. Repeating conditions.

Reaction scheme

Outcome

784.3 mg, 3.48 mmol, 89%

[KlementineJBS]

01.11.23

1. Added NaAsc (389 mg 1.95 mmol, 0.5 equiv.) and CuI (147 mg, 0.782 mmol, 0.2 equiv.) to a flask
2. Backfilled with N2 x 5
3. Added propargyl alcohol (0.28 mL, 4.69 mmol, 1.2 equiv.) and 1-azidonapthyl (661 mg, 3.91 mmol) dissolved in MeCN (10 mL) left stirring at rt from 4 pm
4. Added DIPEA (7.82 mmol) at 5ish (forgot it previously)

[KlementineJBS]

Reaction still not complete but seeing formation of second spot near baseline as in #151. Worked up anyway - 3 x 25 mL DCM, washed with water (25 mL) and brine (25 mL) and dried over mag sulphate.

Crude vial tare: 15.5800 Crude vial full: 16.8538 Mass: 1.2738 g (over 100%)

[KlementineJBS]

H NMR

Actually looks pretty good. Triturating with ether and putting on hivac to see if I can get a proper yield.

KBS28-7 cr.pdf KBS28-7 cr_1.zip

[KlementineJBS]

H NMR

Looks pretty similar after trituration, but MeCN peak is now gone.

KBS28-7 cr repeat_1.zip KBS28-7 cr.pdf

[KlementineJBS]

H NMR

Did an EDTA wash (2 x 25 mL of 50 mM EDTA in water) and dried, rotovapped down. Looks far better on NMR and now has a reasonable yield.

KBS28-7 after EDTA wash.pdf KBS28-7 repeat 2_1.zip

empty vial: 15.5408 full vial: 16.3251 mass: 784.3 mg, 3.48 mmol, 89%