Cesium carbonate → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

HRID 1990247Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@H:13]2[CH2:17][CH2:16][O:15][CH2:14]2)[CH:11]=1)[C:5]([O:7]C)=[O:6].[N:18]1([C:22]([C:24]2[CH:29]=[CH:28][C:27](Br)=[CH:26][N:25]=2)=[O:23])[CH2:21][CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.O>[N:18]1([C:22]([C:24]2[N:25]=[CH:26][C:27]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@H:13]4[CH2:17][CH2:16][O:15][CH2:14]4)[CH:11]=3)[C:5]([OH:7])=[O:6])=[CH:28][CH:29]=2)=[O:23])[CH2:21][CH2:20][CH2:19]1

Participants

Conditions

Temperature: 160 °C

Procedure

Methyl 3-hydroxy-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate (875 mg, 3.68 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (1.06 g, 4.41 mmol), caesium carbonate (3.59 g, 11.03 mmol), and bromotris(triphenylphosphine)copper (0.69 g, 0.735 mmol) were added together in DMA (16 mL) and heated in a microwave reactor at 160° C. for 9 hours. The mixture was taken up in water (25 mL) and washed with ethyl acetate (2×20 mL). The aqueous layer was acidified with 1N hydrochloric acid (30 mL) and extracted with ethyl acetate (5×30 mL). The combined organic extract was washed with water (30 mL), brine (30 mL), dried (MgSO4), filtered and evaporated to give a brown solid which was triturated with diethyl ether to give the desired compound as a beige solid (820 mg).

Workup

washwashed with ethyl acetate (2×20 mL)
extractionextracted with ethyl acetate (5×30 mL)
extractionThe combined organic extract
washwas washed with water (30 mL), brine (30 mL)
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated
customto give a brown solid which
customwas triturated with diethyl ether

Sources & evidence

ORD record: ord-5bd27331d0bc4680a0729e0dcf74f6a8
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07642259B2

Reaction notes

Loading…