Water → Tert-butyl 4-((2-(cyanomethyl)-6-methoxyphenoxy)methyl)piperidine-1-carboxylate

HRID 253236

Reaction equation

HRID 253236 reaction equation
[OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:10][C:11]#[N:12].CS(O[CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.[Cl-].[Na+].O.C(OCC)(=O)C>[C:11]([CH2:10][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH3:9])[C:2]=1[O:1][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:21][CH2:20]1)#[N:12]

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 1426432-Hydroxy-3-methoxyphenylacetonitrileHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylate

Product 1

HCID 66890287Tert-butyl 4-((2-(cyanomethyl)-6-methoxyphenoxy)methyl)piperidine-1-carboxylateYield 81%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H).

Workup

  1. temperaturecooled to rt
  2. customThe layers were partitioned
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

Sources & evidence

ORD record
ord-13b83ae05be84708ac1b04dd2c0f93b5
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Linked notes

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