Ethanol → 4-[5-Amino-6-(4,4-dimethyl-1-cyclohexen-1-yl)-2-pyridinyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester

HRID 2367835Notes

Reaction equation

HRID 2367835 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16](Br)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22]CO.C([O-])([O-])=O.[Na+].[Na+].[C:31]1([CH3:37])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CCOC(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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([C:34]3[CH2:35][CH2:36][C:31]([CH3:22])([CH3:37])[CH2:32][CH:33]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 1140TolueneHCID 10340Sodium CarbonateHCID 591286051,1-Dimethylethyl 4-(5-amino-6-bromo-2-pyridinyl)-1-piperidinecarboxylate

Product 1

HCID 591286004-[5-Amino-6-(4,4-dimethyl-1-cyclohexen-1-yl)-2-pyridinyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl esterYield 66%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 209 mg (0.587 mmol) 5-amino-6-bromo-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (as prepared in the previous step) in 5 mL of toluene and 2.5 mL of EtOH was treated with 99.3 mg (0.645 mmol) 4,4-dicyclohex-1-enylboronic acid and 2.34 mL (4.69 mmol) 2 M aqueous Na2CO3. The mixture was degassed via sonication, placed under argon, treated with 47.4 mg (0.0410 mmol) Pd(PPh3)4, and heated to 80° C. for 16 h. The mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with additional EtOAc, and the combined organic layers were dried over MgSO4 and concentrated in vacuo. Chromatography of the residue on a 50-g silica Varian MegaBond Elut column with 25% EtOAc-hexanes afforded 150 mg (66%) of the title compound as a white foamy solid. Mass spectrum (ESI, m/z): Calcd. for C23H35N3O2, 386.3 (M+H). found 386.3.

Workup

  1. customThe mixture was degassed via sonication
  2. washwashed with water
  3. extractionThe aqueous layer was extracted with additional EtOAc
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4edb3d7c793144b39b6d3952496ca559
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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