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

HRID 423593Notes

Reaction equation

HRID 423593 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.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>[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 63%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

4-Bromo-2-fluorobenzeneboronic acid (0.69 g, 3.10 mmol) was added to a solution of 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (1.0 g, 2.70 mmol) in DME (30 mL), followed by addition of 2M Na2CO3 (8 mL) and Pd(PPh3)4 (0.16 g, 0.13 mmol). The reaction mixture was degassed with N2 and heated at 80° C. for 4 h, then cooled to ambient temperature. Water was added and the mixture was extracted with EtOAc (70 mL×2). The combined organic extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product. The crude product was purified by chromatography on a silica gel column eluted with 1:5 EtOAc/hexanes to give 0.785 g (63%) of 1,1-dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J=2.6 Hz), 7.90-7.85 (m, 1H), 7.75-7.65 (m, 1H), 7.40-7.30 (m, 2H), 7.30-7.20 (m, 1H), 4.18 (bs, 2H), 3.89 (d, 2H, J=6.3 Hz), 2.85-2.70 (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 m/z 465/467 (M+H).

Workup

  1. customThe reaction mixture was degassed with N2
  2. temperaturecooled to ambient temperature
  3. additionWater was added
  4. extractionthe mixture was extracted with EtOAc (70 mL×2)
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customto give the crude product
  11. customThe crude product was purified by chromatography on a silica gel column
  12. washeluted with 1:5 EtOAc/hexanes

Sources & evidence

ORD record
ord-3009e1df57c646f79907bc1ac8f490db
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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