Ethyl 4-piperidinecarboxylate → HCID 69025828, compound

HRID 1433095Notes

Reaction equation

HRID 1433095 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](Br)=[CH:5][N:4]=1.[NH:10]1[CH2:20][CH2:19][CH:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:11]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C(OCC)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH2:17]([O:16][C:14]([CH:13]1[CH2:19][CH2:20][N:10]([C:6]2[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[CH2:11][CH2:12]1)=[O:15])[CH3:18]

Participants

8

Reactant 4

HCID 70770Ethyl 4-piperidinecarboxylateHCID 634876Binap, (A+-)-HCID 27348955-Bromo-2-methoxypyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 69025828HCID 69025828, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

In a round-bottom flask, 20 ml of anhydrous toluene is added and degassed several times from vacuum/N2. 2-methoxy-5-bromopyridine (752 mg, 4.0 mmol), ethyl isonipecotate (740 mg, 4.8 mmol), sodium t-butoxide (537 mg, 5.6 mmol), Pd2(DBA)3 (73 mg, 2 mol %) and of BINAP (100 mg, 0.16 mmol) are added and heated to 70° C. under N2 for 16 hrs. The reaction is cooled to r.t. and taken up in 100 ml of ethyl ether and washed with brine (2×50 ml). The ether is dried over MgSO4, filtered and reduced to an oil under vacuum. The compound is purified by flash chromatography on silica gel using 20% ethyl acetate/hexane as the eluent to provide 6′-methoxy-3,4,5,6-tetrahydro-2H-[1,3′]bipyridinyl-4-carboxylic acid ethyl ester. 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H), 7.28 (dd, 1H), 6.66 (d, 1H), 4.15 (q, 2H), 3.87 (s, 3H), 3.42 (dt, 2H), 2.71 (dt, 2H), 2.39 (m, 1H), 2.03 (m, 2H), 1.90 (m, 2H), 1.26 (t, 3H); MS (EI) 264 (M)+.

Workup

  1. customdegassed several times from vacuum/N2
  2. temperatureThe reaction is cooled to r.t.
  3. washwashed with brine (2×50 ml)
  4. dry with materialThe ether is dried over MgSO4
  5. filtrationfiltered
  6. customThe compound is purified by flash chromatography on silica gel using 20% ethyl acetate/hexane as the eluent

Sources & evidence

ORD record
ord-4d8358b75e504e3bb050f552a1afbadc
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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