Hydrochloric Acid → 6-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionylamino]-nicotinic acid

HRID 398602Notes

Reaction equation

C[O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:27])[C@@H:12]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.Cl>O1CCCC1.O>[CH:14]1([CH2:13][C@H:12]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:28])=[O:2])=[CH:5][N:6]=2)=[O:27])[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 6-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionylamino]-nicotinic acid methyl ester (prepared as in Example 45, 188 mg, 0.45 mmol) in tetrahydrofuran (3 mL) was treated with a 3N aqueous hydrochloric acid solution (3 mL). The resulting reaction mixture was heated under reflux at 60° C. for 4 h. After such time, the reaction was cooled to 25° C., diluted with water (5 mL), and then extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate with 1% acetic acid) afforded 6-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionylamino]-nicotinic acid (8 mg, 4%) as a white solid: [α]23589=−41.4° (c=0.099, chloroform); FAB-HRMS m/e calcd for C20H20Cl2N2O3 (M+H)+ 407.0930, found 407.0928.

Workup

customThe resulting reaction mixture
temperaturewas heated
temperatureAfter such time, the reaction was cooled to 25° C.
extractionextracted with ethyl acetate (3×20 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b1d285057d6a40f0a9c02b7004f070aa
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610846B1

Reaction notes

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