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

HRID 1014872

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-458decd3ac8a427b856a65e5d7091027
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981913B2

Linked notes

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