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11th January 2012 @ 03:31
Product obtained in 63% yield.

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Coupling of Boc-protected glycine and 4-aminoantipyrine using T3P. Repeat of PMY 29-1

Reaction Scheme

Reaction start time: 16.00 11/01/12
Boc-Gly-OH (500 mg, 2.85 mmol, 1 equiv.) and 4-aminoantipyrine (638 mg, 3.14 mmol, 1.1 equiv.) were dissolved in DMF (2.5 mL) and pyridine (1.30 mL, 16.14 mmol, 5.65 equiv.). The mixture was cooled in an ice/bath and T3P (50 wt.% in EtOAc, 3.1 mL, 4.9 mmol, 1.7 equiv.) was added. The mixture was allowed to warm to room temperature and the mixture overnight. After 21 hours, TLC shows reaction complete. Water (30 mL) added and the mixture stirred for 20 minutes. The pH 5 solution was extracted with EtOAc (3 × 20 mL). The extracts were washed with water (3 × 20 mL) and brine then dried (MgSO4) and concentrated under reduced pressure to a yellow/white solid, PMY 29-2-A (560 mg). 10% NaHCO3 added to aqueous until pH 8. Extracted with EtOAc (2 × 30 mL). Combined extracts washed with water (3 × 20 mL) and brine then dried (MgSO4) and concentrated under reduced pressure to a orange oil. Crystallised on standing to a yellow/white solid, PMY 29-2-B (240 mg). PMY 29-2-A dissolved in water (approx 15 mL) and 10% NaHCO3 added until pH 8. Extracted with EtOAc (3 × 20 mL). The combined extracts were washed with water (15 mL), brine then dried (MgSO4) and concentrated to a white/yellow solid (406 mg). Total yield 646 mg, 63%. 1H NMR of both PMY 29-2-A and -B are a reasonable match at pH 8. 13C NMR consistent with expected product (traces of residual acetone from insufficiently dried tube).

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 21 hours

Mini-work up:Drop of reaction mixture quenched with water and partitioned with EtOAc. Potential for SM to have remained in aqueous.

NMR:
1H NMR PMY 29-2-B
PMY 29-2-A
1H NMR crude
1H and 13C NMR


Risk and Hazard Assessment:
As for, Synthesis of TCMDC-123812 using T3P (PMY 10-4)

See also:
Coupling of Boc-Gly-OH and 4-aminoantipyrine (PMY 29-1)
Hydrolysis of benzoyl protected glycinamide PMY 27-1 (PMY 28-2)
Hydrolysis of benzoyl protected glycinamide PMY 27-1 (PMY 28-1)
Coupling of hippuric acid and 4-aminoantipyrine using T3P (PMY 27-1)

InChI=1S/C18H24N4O4/c1-12-15(20-14(23)11-19-17(25)26-18(2,3)4)16(24)22(21(12)5)13-9-7-6-8-10-13/h6-10H,11H2,1-5H3,(H,19,25)(H,20,23)
Linked Entries
Attached Files
TLC 21 hours
1H NMR crude
1H NMR PMY 29-2-B
PMY 29-2-A
1H and 13C NMR
Comments