Ethyl Acetate → 3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid

HRID 20949

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]([N:14]2[CH2:18][CH2:17][CH2:16][C@@H:15]2[CH2:19][O:20][CH3:21])=[O:13])[CH:11]=1)[C:5]([O:7]C)=[O:6].C([Sn](CCCC)(CCCC)[C:27]1[O:28][CH:29]=[CH:30][N:31]=1)CCC.C(OCC)(=O)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:21][O:20][CH2:19][C@H:15]1[CH2:16][CH2:17][CH2:18][N:14]1[C:12]([C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([C:27]2[O:28][CH:29]=[CH:30][N:31]=2)[CH:11]=1)[C:5]([OH:7])=[O:6])=[O:13]

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate (Step H (1), 350 mg, 1.0 mmol) in dioxane (5 mL) were added Pd(PPh3)4 (173.5 mg, 0.15 mmol) and 2-(tributylstannyl)oxazole (1.8 g, 5.0 mmol) above made and the reaction mixture was stirred at 95° C. with sealed cap for 16 h. Ethyl acetate (200 mL) was added and the mixture was washed with H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 30% to 50% to 70% EtOAc/Hexane step gradient) to give 250 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ ppm 1.75-2.11 (4H, m), 3.08 (1H, brd s), 3.38 (3H, s), 3.50 (1H, m), 3.63 (2H, s), 3.83 (3H, s), 4.43 (1H, s), 7.24 (1H, s), 7.73 (1H, s), 8.22 (1H, s), 8.35 (1H, s), 8.71 (1H, s). MS (ESI) (M+H)+ 345.26.

Workup

customwith sealed
customcap for 16 h
washthe mixture was washed with H2O
concentrationconcentrated under vacuum
customThe crude mixture was purified by silica gel Flash Chromatography (0% to 30% to 50% to 70% EtOAc/Hexane step gradient)

Sources & evidence

ORD record: ord-fac2b34946504af08e86ea66659978ea
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745470B2

Linked notes

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