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13th March 2012 @ 06:15
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Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium triacetoxyborohydride as reductant. 38-1 gave mainly the alcohol. A milder reducing agent should help here.

38-2.png

Reaction Start Time: 11.10 14/03/12
Glycinamide hydrochloride (132 mg, 1.20 mmol, 1.3 equiv.) was stirred in DCM (40 mL). Triethylamine (0.17 mL, 1.20 mmol, 1.3 equiv.) was added and the mixture stirred for 10 minutes. Reaction turns briefly hazy. aldehyde PMY 2-5 (200 mg, 0.92 mmol, 1 equiv.) was added followed by freshly activated molecular sieves. The reaction stirred for 5 minutes. Sodium triacetoxyborohydride (214 mg, 1.01 mmol, 1.1 equiv.) was added and the reaction left to stir at room temperature. After 2 hours, the reaction is still a hazy solution/suspension. TLC shows mainly starting material, no reduced aldehyde, minor polar spot (red stain). A few drops (4-5) of glacial acetic acid were added and stirring continued. After 3 hours, TLC shows no major change, potentially some more conversion. After overnight reaction, still no change by TLC. A further portion of AcOH (0.3 mL) was added. After a further 7 hours, a small amount of reduced aldehyde is observed on TLC. No further change overnight (16/03/12). Reaction filtered through celite and 10% NaHCO3 (30 mL) added to the filtrate.

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 2 hours
TLC 3 hours


NMR:
1H NMR precipitate
1H NMR


Risk and Hazard Assessment:
See: Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination (PMY 38-1)

Reference:
doi:10.1021/jo960057x
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Scheme
Scheme updated
TLC 2 hours
TLC 3 hours
1H NMR precipitate
1H NMR