Triethylamine → Ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate

HRID 241442Notes

Reaction equation

HRID 241442 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]([CH:10]([F:12])[F:11])=[N:8][CH:9]=1.C(=O)(OC(C)(C)C)[O:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=O.C(N(CC)CC)C>C1COCC1>[C:23]([O:22][C:20]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]([CH:10]([F:12])[F:11])=[N:8][CH:9]=1)=[O:19])([CH3:26])([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 71059730Ethyl 5-(aminomethyl)-2-(difluoromethyl)nicotinate hydrochloride

Product 1

HCID 71059899Ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Combine ethyl 5-(aminomethyl)-2-(difluoromethyl)pyridine-3-carboxylate hydrochloride (17.849 mmol, 4.760 g), THF (180 mL) and tert-butoxycarbonyl tert-butyl carbonate (21.419 mmol, 4.675 mL). Stir the mixture at room temperature for about 10 minutes. Add triethylamine (5.225 mL, 37.484 mmol), and stir at room temperature 16 hours. Remove the solids by vacuum filtration, and rinse with EtOAc. Concentrate the filtrate under reduced pressure. Purify the resulting yellow oil by silica gel chromatography (220 g RediSep® silica gel column) eluting with a gradient of 5-45% EtOAc gradient in hexane to give the title compound (3.62 g, 68% yield) as a light yellow crystalline solid. 1H NMR (399.80 MHz, d6-DMSO) δ 8.71 (d, J=2.1 Hz, 1H), 8.15-8.13 (m, 1H), 7.56-7.24 (m, 2H), 4.33 (q, J=7.1 Hz, 2H), 4.24-4.21 (m, 2H), 1.36 (s, 9H), 1.30 (t, J=7.1 Hz, 3H). LCMS (m/z) 331 (M+1).

Workup

  1. customRemove the solids
  2. filtrationby vacuum filtration
  3. washrinse with EtOAc
  4. concentrationConcentrate the filtrate under reduced pressure
  5. customPurify the resulting yellow oil by silica gel chromatography (220 g RediSep® silica gel column)
  6. washeluting with a gradient of 5-45% EtOAc gradient in hexane

Sources & evidence

ORD record
ord-449e0ecfcae74e8292e1aef766185c91
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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