Sodium Carbonate → 1,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate

HRID 423519Notes

Reaction equation

HRID 423519 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([F:11])[CH:3]=1.Br[C:13]1[N:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[N:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]3)=[CH:15][CH:14]=2)=[C:4]([F:11])[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27733334-Bromo-2-fluorobenzeneboronic acidHCID 579302011,1-Dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate

Product 1

HCID 666731501,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylateYield 41.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

1,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate (0.23 g, ˜90% purity, 42%) was prepared as a white solid from (4-bromo-2-fluorophenyl)boronic acid (0.30 g, 1.36 mmol), 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (0.44 g, 1.19 mmol), 2M Na2CO3 (2 mL), and PdCl2(PPh3)2 (85 mg, 0.12 mmol) in DME (4 mL) in a manner similar to Example 21, Step 3. The material was purified by chromatography on a silica gel column eluted with 20% EtOAc/hexanes. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J=2.7 Hz), 7.90-7.85 (m, 1H), 7.72 (d, 1H, J=8.8 Hz), 7.45-7.30 (m, 2H), 7.30-7.25 (m, 1H), 4.25-4.10 (m, 2H), 3.99 (d, 2H, J=6.4 Hz), 2.95-2.80 (m, 2H), 2.05-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.35-1.25 (m, 2H); LRMS (ESI), m/z 465/467 (M+H).

Workup

  1. customThe material was purified by chromatography on a silica gel column
  2. washeluted with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-d0a41b97faa3412eb347223e53334f5f
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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