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

HRID 1869636Notes

Reaction equation

HRID 1869636 reaction equation
[CH3:1][CH:2]([N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH2:6][CH2:5]1)[CH3:3].Br[C:18]1[CH:19]=[CH:20][C:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:22][CH:23]=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>[CH3:3][CH:2]([N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([C:18]3[CH:19]=[CH:20][C:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:22][CH:23]=3)[CH2:15][CH2:16]2)[CH2:6][CH2:5]1)[CH3:1]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 24997839tert-Butyl 5-bromopyridine-2-carboxylateHCID 688858081-(1-Methylethyl)-4-(4-piperidinylmethyl)piperidine

Product 1

HCID 116898931,1-Dimethylethyl 5-(4-{[1-(1-methylethyl)-4-piperidinyl]methyl}-1-piperidinyl)-2-pyridinecarboxylateYield 55.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-(1-Methylethyl)-4-(4-piperidinylmethyl)piperidine (may be prepared as described in Description 4) (0.25 g), 1,1-dimethylethyl 5-bromo-2-pyridinecarboxylate (may be prepared as described in Description 12) (0.29 g), BINAP (0.06 g) and Cs2CO3 (1.82 g) were added to toluene (50 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, degassed again, and the reaction mixture heated at 100° C. for 24 h. The reaction mixture was filtered and evaporated, after which chromatography (silica gel, eluting with methanol/dichloromethane, 0-20%) afforded the title compound (E4) as a yellow solid (0.25 g). MS electrospray (+ion) 424 (MNa+)

Workup

  1. customthe reaction mixture degassed by sequential freezing in dry ice
  2. additionwas added
  3. customdegassed again
  4. temperaturethe reaction mixture heated at 100° C. for 24 h
  5. filtrationThe reaction mixture was filtered
  6. customevaporated
  7. washafter which chromatography (silica gel, eluting with methanol/dichloromethane, 0-20%)

Sources & evidence

ORD record
ord-e51c80b53ccb49b095f7e159614817d9
Source dataset
uspto-grants-2009_12
Patent number
US07638631B2

Reaction notes

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