Potassium Phosphate, Tribasic → 4-(4-Amino-3-cyclohex-1-enyl-phenyl)-1-methyl-piperidine-2,6-dione

HRID 340567Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[CH2:9]2)=[CH:4][C:3]=1Br.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:26]1(B(O)O)[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[CH2:9]2)=[CH:4][C:3]=1[C:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 265 mg (0.892 mmol) of 4-(4-amino-3-bromo-phenyl)-1-methyl-piperidine-2,6-dione (as prepared in the previous step) in toluene (15 mL) and dioxane (15 mL) was treated with 379 mg (1.78 mmol) of K3PO4, 146 mg (1.16 mmol) of cyclohex-1-enylboronic acid, and 125 mg (0.357 mmol) of 2-(dicyclohexylphosphino)-biphenyl. The mixture was degassed via sonication, placed under Ar, treated with 20.0 mg (0.00892 mmol) of Pd(OAc)2, and heated to 80° C. for 2.5 h. The mixture was diluted with EtOAc (70 mL) and washed with water (2×50 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 25-50% EtOAc-hexane afforded 266 mg (100%) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C18H22N2O2, 299.2 (M+H). found 299.1.

Workup

customThe mixture was degassed via sonication
washwashed with water (2×50 mL)
dry with materialThe combined organic layers were dried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-758a398285d249ea85135db61f87685c
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895584B2

Reaction notes

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