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

HRID 423512Notes

Reaction equation

HRID 423512 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Cl[C:15]1[N:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:15]2[N:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]3[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:27][CH2:28]3)=[CH:17][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 59718534tert-Butyl 4-{[(6-chloropyridin-3-yl)oxy]methyl}piperidine-1-carboxylate

Product 1

HCID 249943331,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

The title compound was prepared as a white solid from [4-(methylsulfonyl)phenyl]boronic acid (0.44 g, 2.15 mmol), 1,1-dimethylethyl 4-{[(6-chloro-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (0.54 g, 1.65 mmol), 2M Na2CO3 (5 mL) and PdCl2(PPh3)2 (0.12 g) in DMF (20 mL). The reaction mixture was heated at 85° C. under N2 for 5 h, then cooled to ambient temperature, and extracted with EtOAc (70 mL×2). The combined organic extracts were washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a gray solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 to give the title compound (0.44 g, 60%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.36 (d, 1H, J=2.9 Hz), 8.18 (d, 2H, J=8.6 Hz), 8.02 (d, 2H, J=8.3 Hz), 7.92 (d, 1H, J=8.8 Hz), 7.49 (dd, 1H, Ja=8.8 Hz, Jb=2.9 Hz), 4.20-4.10 (m, 2H), 3.99 (d, 2H, J=6.3 Hz), 3.15 (s, 3H), 2.90-2.75 (m, 2H), 2.10-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.35-1.25 (m, 2H); LRMS (ESI), m/z 447 (M+H).

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted with EtOAc (70 mL×2)
  3. washThe combined organic extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give the crude product as a gray solid

Sources & evidence

ORD record
ord-aede753b0707466bac6faf774886a1d1
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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