Water → methyl (S)-2-cyclopropylmethoxy-3-[3'-(methylamino)biphenyl-4-yl]propanoate

HRID 1009222Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)[C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:19][NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CN(C)C=O.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>[CH:16]1([CH2:15][O:14][C@@H:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([NH:20][CH3:19])[CH:22]=3)=[CH:3][CH:4]=2)[C:10]([O:12][CH3:13])=[O:11])[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 90 °C

Procedure

53 mg (0.046 mmol) of tetrakis(triphenylphosphine)palladium are added to a solution of 145 mg (0.46 mmol) of methyl (S)-3-(4-bromophenyl)-2-(cyclopropylmethoxy)propionate and 129 mg (0.55 mmol) of methyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine in 3 ml of dimethylformamide. 0.3 ml of a 2M potassium phosphate solution is added and the reaction mixture is stirred at 90° C. for 2 hours. The reaction is halted by the addition of 10 ml of water and then extraction is carried out with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated and then the residue is chromatographed on silica gel (heptane/ethyl acetate 80/20). 70 mg of methyl (S)-2-cyclopropylmethoxy-3-[3′-(methylamino)biphenyl-4-yl]propanoate are obtained in the form of an oil. Yield=45%.

Workup

extractionextraction
dry with materialdried over sodium sulfate
customThe solvents are evaporated
customthe residue is chromatographed on silica gel (heptane/ethyl acetate 80/20)

Sources & evidence

ORD record: ord-cfbcca531459448da90bca1d35b9367b
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973063B2

Reaction notes

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