p-Bromophenyl octyl ether → 2-[4-(Octyloxy)-phenyl]-5-[(tetrahydro-2-pyranyloxy)methyl]pyridine

HRID 1030028

Reaction equation

HRID 1030028 reaction equation
[Mg].[CH2:2]([O:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].Cl[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][O:28]2)=[CH:21][N:20]=1.C(=O)([O-])O.[Na+]>C(OCC)C.CC(P(C1C=CC=CC=1)C1C=CC=CC=1)C.C1C=CC(PC2C=CC=CC=2)=CC=1.[Cl-].[Ni].O1CCCC1>[CH2:2]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)=[CH:21][N:20]=2)=[CH:13][CH:12]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]

Participants

8

Reactant 4

HCID 145298p-Bromophenyl octyl etherHCID 516892Sodium BicarbonateHCID 5462224MagnesiumHCID 221273782-Chloro-5-{[(oxan-2-yl)oxy]methyl}pyridine

Product 1

HCID 198212452-[4-(Octyloxy)-phenyl]-5-[(tetrahydro-2-pyranyloxy)methyl]pyridineYield 67.2%

Reagents, catalysts & solvents 3

HCID 21654969Diphenylphosphane;diphenyl(propan-2-yl)phosphane;nickel;chlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A Grignard reagent solution prepared from 0.8 g of magnesium, 10.3 g of (4-bromophenyl) octyl ether and 50 ml of tetrahydrofuran was added dropwise at 0°-5° C. within 30 minutes to a mixture of 7.5 g of crude 2-chloro-5-[(tetrahydro-2-pyranyloxy)methyl]pyridine, 75 ml of tetrahydrofuran and 0.36 g of 1,3-bis(diphenylphosphino)-propanenickel-(II) chloride. The reaction mixture was stirred for 3 hours, left to stand overnight, then adjusted to pH 8 with aqueous sodium hydrogen carbonate solution and diluted with diethyl ether. The organic phase was washed neutral with water, dried over sodium sulfate and concentrated. Chromatographic purification of the residue (14.6 g) on 210 g of silica gel with hexane/ethyl acetate (vol. 4:1) yielded 8.8 g of 2-[4-(octyloxy)-phenyl]-5-[(tetrahydro-2-pyranyloxy)methyl]pyridine.

Workup

  1. waitleft
  2. waitto stand overnight
  3. washThe organic phase was washed neutral with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customChromatographic purification of the residue (14.6 g) on 210 g of silica gel with hexane/ethyl acetate (vol. 4:1)

Sources & evidence

ORD record
ord-353edb4686bd4b7699d7958b0d957b13
Source dataset
uspto-grants-1992_04
Patent number
US05104569

Linked notes

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