Triphenylphosphine → 3-(2-Amino-5-bromo-pyridin-3-yloxy)-2,2-dimethylpropionic acid methyl ester

HRID 1879959Notes

Reaction equation

HRID 1879959 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.[CH3:10][C:11]([CH3:18])([CH2:16]O)[C:12]([O:14][CH3:15])=[O:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+](C(OCC)=O)(C(OCC)=O)=[N-]>C1COCC1>[CH3:15][O:14][C:12](=[O:13])[C:11]([CH3:18])([CH3:16])[CH2:10][O:8][C:7]1[C:2]([NH2:1])=[N:3][CH:4]=[C:5]([Br:9])[CH:6]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 84152Methyl 3-hydroxypivalateHCID 116940412-Amino-5-bromo-3-hydroxypyridineHCID 14357405Diethyldiazodicarboxylate

Product 1

HCID 593328383-(2-Amino-5-bromo-pyridin-3-yloxy)-2,2-dimethylpropionic acid methyl esterYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-amino-5-bromopyridin-3-ol (1.42 g, 7.51 mmol) in THF (40 mL) was added methyl 2,2-dimethyl-3-hydroxypropionate (1.2 mL, 9.0 mmol) and triphenyl phosphine (2.36 g, 9.00 mmol). The mixture was cooled to 0° C., then treated with diethyl diazodicarboxylate (1.70 g, 9.75 mmol). The mixture was heated in microwave at 120° C. for 20 min. The solvent was concentrated, and the residue was purified by chromatography (silica gel, hexanes/EtOAc, 75:25 to 60:40) to give the title compound (0.88 g, 39%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J=2.1 Hz, 1H), 7.02 (d, J=2.1 Hz, 1H), 4.65 (br s, 2H), 3.96 (s, 2H), 3.71 (s, 3H), 1.34 (s, 6H); ESI MS m/e 303 (M+H)+.

Workup

  1. temperatureThe mixture was heated in microwave at 120° C. for 20 min
  2. concentrationThe solvent was concentrated
  3. customthe residue was purified by chromatography (silica gel, hexanes/EtOAc, 75:25 to 60:40)

Sources & evidence

ORD record
ord-769e16f0811348eb911b56a66cb37b94
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

Loading…