Nicotinic Acid → Glycine, N-(3-pyridinylcarbonyl)-, methyl ester

HRID 1803407Notes

Reaction equation

[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:28][O:29][C:30](=[O:33])[CH2:31][NH2:32]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(Cl)(Cl)Cl>[CH3:28][O:29][C:30](=[O:33])[CH2:31][NH:32][C:1]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)=[O:9]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of nicotinic acid (10 g, 81 mmol), p-toluenesulfonyl chloride (17 g, 89 mmol), benzyltriethylammonium chloride (1.85 g, 8.1 mmol), and potassium carbonate (K2CO3, 44.9 g, 320 mmol) in chloroform (CHCl3, 500 mL) was stirred mechanically at 40° C. for 1 h. Glycine methyl ester hydrochloride (10.2 g, 81 mmol) and K2CO3 (11.2 g, 80 mmol) were then added and stirred at 50° C. for 90 minutes (min). The reaction mixture was filtered through Celite® and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (2% methanol/ethyl acetate) to give the desired product as an orange gum which solidified upon standing at room temperature (4.7 g, 30%): 1H NMR (400 MHz, CDCl3) δ 9.04 (d, J=2.2 Hz, 1H), 8.76 (dd, J=4.8, 1.5 Hz, 1H), 8.15 (dt, J=8.1, 1.8 Hz, 1H), 7.42 (dd, J=8.1, 4.8 Hz, 1H), 6.84 (br s, 1H), 4.28 (d, J=5.2 Hz, 2H), 3.87 (s, 3H); ESIMS m/z 195 (M+1).

Workup

stirringstirred at 50° C. for 90 minutes (min)
filtrationThe reaction mixture was filtered through Celite®
concentrationthe filtrate was concentrated under reduced pressure
customThe crude product was purified by silica gel column chromatography (2% methanol/ethyl acetate)

Sources & evidence

ORD record: ord-53ac98e4b64f404d9127625d6634c9c0
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08350044B2

Reaction notes

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