Cesium carbonate → 1,1-Dimethylethyl 5-{4-[(1-cyclobutyl-4-piperidinyl)methyl]-1-piperidinyl}-2-pyridinecarboxylate

HRID 1869635Notes

Reaction equation

HRID 1869635 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][CH:8]([CH2:11][CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Br[C:19]1[CH:20]=[CH:21][C:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:23][CH:24]=1.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([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH:1]1([N:5]2[CH2:6][CH2:7][CH:8]([CH2:11][CH:12]3[CH2:17][CH2:16][N:15]([C:19]4[CH:20]=[CH:21][C:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:23][CH:24]=4)[CH2:14][CH2:13]3)[CH2:9][CH2:10]2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 24997839tert-Butyl 5-bromopyridine-2-carboxylateHCID 688867961-Cyclobutyl-4-(4-piperidinylmethyl)piperidine

Product 1

HCID 116257881,1-Dimethylethyl 5-{4-[(1-cyclobutyl-4-piperidinyl)methyl]-1-piperidinyl}-2-pyridinecarboxylateYield 26.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-Cyclobutyl-4-(4-piperidinylmethyl)piperidine (may be prepared as described in Description 6) (0.50 g), 1,1-dimethylethyl 5-bromo-2-pyridinecarboxylate (may be prepared as described in Description 12) (0.66 g), BINAP (0.15 g) and Cs2CO3 (1.6 g) were added to toluene (20 ml) under argon and the reaction mixture degassed by sequential freezing in dry ice followed by warming to room temp under vacuum (3×). After stirring for 5 min Pd(OAc)2 (0.05 g) was added and the reaction mixture heated at 80° C. for 20 h. The reaction mixture was filtered and evaporated, after which chromatography (silica gel, eluting with methanol/dichloromethane, 0-20%) afforded the title compound (E3) as a solid (0.23 g). MS electrospray (+ion) 414 (MH+)

Workup

  1. customthe reaction mixture degassed by sequential freezing in dry ice
  2. additionwas added
  3. temperaturethe reaction mixture heated at 80° C. for 20 h
  4. filtrationThe reaction mixture was filtered
  5. customevaporated
  6. washafter which chromatography (silica gel, eluting with methanol/dichloromethane, 0-20%)

Sources & evidence

ORD record
ord-57b7d11f17314f49a0a67d4ada931880
Source dataset
uspto-grants-2009_12
Patent number
US07638631B2

Reaction notes

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