Cesium carbonate → [4-(4-Cyanomethoxyphenyl)butyl]carbamic acid tert-butyl ester

HRID 132572Notes

Reaction equation

HRID 132572 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:27][C:28]#[N:29]>CN(C=O)C>[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH2:27][C:28]#[N:29])=[CH:16][CH:17]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 69356IodoacetonitrileHCID 22592408tert-Butyl [4-(4-hydroxyphenyl)butyl]carbamate

Product 1

HCID 21031133[4-(4-Cyanomethoxyphenyl)butyl]carbamic acid tert-butyl esterYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of [4-(4-hydroxyphenyl)butyl]carbamic acid tert-butyl ester 31 (0.365 g, 1.37 mmol) and Cs2CO3 (0.672 g, 2.06 mmol) in anhydrous DMF (8 mL) was heated at 65° C. for 30 min. Iodoacetonitrile (0.276 g, 1.651 mmol) was then added to the mixture in one portion. The mixture was stirred at 65° C. overnight, and then cooled to room temperature. The precipitated solid was filtered, and the filtrate was partitioned between water and dichloromethane (each 50 mL). The organic layer was separated, washed with brine (3×50 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was chromatographed on silica gel, eluting with a mixture of diethyl ether/dichloromethane (6:94, v/v), to afford the desired product 40 (0.109 g, 38% yield) as a colorless viscous oil. 1H NMR (300 MHz, CDCl3): δ 1.43 (s, 9H), 1.57 (m, 4H), 2.60 (t, 2H), 3.15 (m, 2H), 4.49 (br, 1H), 4.75 (s, 2H), 6.91 (d, 2H), 7.13 (d, 2H).

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe precipitated solid was filtered
  3. customthe filtrate was partitioned between water and dichloromethane (each 50 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (3×50 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under vacuum
  8. customThe residue was chromatographed on silica gel
  9. washeluting with a mixture of diethyl ether/dichloromethane (6:94

Sources & evidence

ORD record
ord-13ce0486b5c54e0d999a119051070193
Source dataset
uspto-grants-2008_06
Patent number
US07388013B2

Reaction notes

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