4-(2-Carboxyethyl)benzeneboronic acid → 3-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yl]-propionic acid

HRID 2235298Notes

Reaction equation

FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([CH2:14][CH:15]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:16]2=[O:26])=[C:9]([Cl:27])[CH:8]=1)(=O)=O.[C:30]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)([OH:32])=[O:31]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[Cl:27][C:9]1[CH:8]=[C:7]([C:38]2[CH:39]=[CH:40][C:35]([CH2:34][CH2:33][C:30]([OH:32])=[O:31])=[CH:36][CH:37]=2)[CH:12]=[C:11]([Cl:13])[C:10]=1[CH2:14][CH:15]1[CH2:19][CH2:18][N:17]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[C:16]1=[O:26]

Participants

Conditions

Temperature: 95 °C

Procedure

Charge a vial with 3,5-dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate (Example 240) (0.30 g, 0.63 mmol), 4-(2-carboxyethyl)benzene boronic acid (0.123 g, 0.634 mmol) and Pd(Ph3)4 (0.073 g, 0.063 mmol) in 1,4-dioxane (5 mL) and 2 M Na2CO3 (1 mL) and heat to 95° C. for 16 hours. Cool the reaction, extract with ethyl acetate and water, dry the organic layer (Na2SO4) and purify by HPLC (5 to 95% acetonitrile in water with 0.1% trifluroacetic acid buffer) to afford 373 mg (62%) of the title compound: LC-MS (ES +) m/z=exact mass calcd for C26H29Cl2NO3 473, found 474 and 476 (M+1 and M+3, 100%).

Workup

temperatureCool
customthe reaction
extractionextract with ethyl acetate and water
dry with materialdry the organic layer (Na2SO4)
custompurify by HPLC (5 to 95% acetonitrile in water with 0.1% trifluroacetic acid buffer)

Sources & evidence

ORD record: ord-f3ba82eeb68b4d298201187dc7cb1e67
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07713979B2

Reaction notes

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