(4-Methoxyphenyl)boronic acid → (S)-tert-Butyl 4-(1-cyano-2-(4'-methoxybiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216948Notes

Reaction equation

[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)#[N:2].[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C([O-])(=O)C.[K+]>C(#N)C>[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:34]2[CH:35]=[CH:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=2)=[CH:7][CH:6]=1)#[N:2]

Participants

Conditions

Temperature: 75 °C

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 15, step (i), 317 mg) in acetonitrile (5 mL) under nitrogen was treated with 4-methoxyphenylboronic acid (96 mg) followed by an aqueous solution of potassium acetate (2M, 0.65 mL) and 1,1 bis(bi-tert-butylphosphino)ferrocene palladium dichloride (8 mg). The reaction mixture was stirred at 75° C. for 18 h and then evaporated, dissolved in dichloromethane and absorbed onto silica. Purification by chromatography on silica eluting with 50% ethyl acetate in isohexane and then 100% ethyl acetate afforded the sub-titled compound as a solid (120 mg).

Workup

customevaporated
dissolutiondissolved in dichloromethane
customabsorbed onto silica
customPurification by chromatography on silica eluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-ba36ba764eb143578abd25e442ce6edd
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193239B2

Reaction notes

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