Hydrochloric Acid → 4-{5-[(1R)-2-Amino-1-(carboxymethyl)ethyl]-2-chlorophenyl}benzoic acid hydrochloride
Reaction equation
O=C1NC[C@@H](C2C=CC([Cl:22])=C([C:13]3[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=3)C=2)C1.Cl.Cl.[NH2:25][CH2:26][C@@H:27]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34](Br)[CH:33]=1)[CH2:28][C:29]([OH:31])=[O:30]>>[ClH:22].[NH2:25][CH2:26][C@@H:27]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=2)[CH:33]=1)[CH2:28][C:29]([OH:31])=[O:30]Participants
Procedure
(4R)-4-(3-Bromo-4-chlorophenyl)pyrrolidin-2-one (0.5 g, 0.55 mmol) and 4-methoxycarbonylphenyl boronic acid (0.144 g, 0.55 mmol) were mixed in DMF (2 mL). The mixture was degassed by alternately applying a vacuum and flushing with nitrogen gas. Palladium acetate (0.025 g, 0.11 mmol) and tetrabutylammonium bromide (0.053 g, 0.165 mmol) were added followed by potassium phosphate (0.35 g, 1.65 mmol). The mixture was stirred overnight at 90° C. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), washed with 10% aqueous HCl solution then brine, and concentrated in vacuo to provide 4-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid. 4-[5-((3R)-5-Oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid was then treated with HCl as described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride to provide the title compound (24). MS (ESI) m/z 334.07 (M+H)+.
Sources & evidence
- ORD record
- ord-25654cd90a49420c9fec5e7afe193144
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08344028B2
Reaction notes
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