Water → HCID 66890897, compound

HRID 253232Notes

Reaction equation

HRID 253232 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([O:11][CH3:12])=[O:10])=[CH:5][C:4]=1[OH:13].C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1)(=O)=O.O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([O:11][CH3:12])=[O:10])=[CH:5][C:4]=1[O:13][CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylateHCID 4056967Methyl 3-hydroxy-4-methoxybenzoate

Product 1

HCID 66890897HCID 66890897, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 3-hydroxy-4-methoxy benzoate (2.0 g, 11 mmol) in DMF (25 mL) was added cesium carbonate (7.2 g, 22 mmol) and 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (3.2 g, 11 mmol). The mixture was heated to 70° C. and stirred for 2 h. After cooling to rt, water was added and the resulting aqueous mixture was extracted with ether followed by ethyl acetate. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 3.54 g of 1,1-dimethylethyl 4-[({2-(methyloxy)-5-[(methyloxy)carbonyl]phenyl}oxy)methyl]piperidine-1-carboxylate (9.3 mmol, 85% yield). 1H NMR (400 MHz, CDCl3): δ7.69-7.66 (dd, 1H), 7.52 (d, 1H), 6.88 (d, 1H), 4.15 (br m, 2H), 3.92 (s, 3H), 3.91-3.88 (m, 2H), 3.90 (s, 3H), 2.76 (br m, 2H), 2.06 (m, 1H), 1.88 (br d, 2H), 1.47 (s, 9H), 1.31-1.25 (m, 2H); MS (EI) for C20H29NO6: 402 (MNa+).

Workup

  1. temperatureAfter cooling to rt
  2. extractionthe resulting aqueous mixture was extracted with ether
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

Sources & evidence

ORD record
ord-f1bc32071d8347ee9a80064950a1637e
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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