Nitrogen → tert-Butyl 4-(4-((tert-butoxycarbonyl)amino)-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2272445Notes

Reaction equation

HRID 2272445 reaction equation
FC(F)(F)S(O[C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]=1)(=O)=O.[F:22][C:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:24]=1[NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].N#N.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[C:41]([O:40][C:39]([NH:38][C:24]1[CH:25]=[CH:26][C:27]([C:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9][CH:8]=2)=[CH:28][C:23]=1[F:22])=[O:45])([CH3:44])([CH3:42])[CH3:43]

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 22346775Tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenylcarbamate

Product 1

HCID 68283496tert-Butyl 4-(4-((tert-butoxycarbonyl)amino)-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of tert-butyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate (I16) (0.504 g, 1.52 mmol), tert-butyl (2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (I62) (0.496 g, 1.47 mmol), and PdCl2(PPh3)2 (0.055 g, 0.078 mmol) under a N2 atmosphere was added dioxane (15 mL) and the mixture was bubbled with N2 for 5 minutes before addition of 3.0 M aqueous sodium carbonate (1.5 mL, 4.5 mmol). The reaction was heated at reflux for 6 hours then concentrated under reduced pressure. The residue was chromatographed on silica gel (0-25% EtOAc/petroleum benzine 40-60° C.) to give the title compound (I57) (0.409 g, 71%); 1H NMR (400 MHz, CDCl3) δ 7.12 (m, 3H), 6.09 (s, 1H), 4.08 (m, J=2.8 Hz, 2H), 3.63 (dd, J=5.6, 5.6 Hz, 2H), 2.49 (m, 2H), 1.42 (s, 18H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 6 hours
  3. concentrationthen concentrated under reduced pressure
  4. customThe residue was chromatographed on silica gel (0-25% EtOAc/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-4326017d988643918281e0a03e3cdc49
Source dataset
uspto-grants-2015_09
Patent number
US09120761B2

Reaction notes

Loading…