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

HRID 2218068Notes

Reaction equation

HRID 2218068 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:20]([O-])([O-])=O.[Cs+].[Cs+].C[N:27]([CH:29]=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][CH2:20][C:29]#[N:27])=[CH:16][CH:17]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 22592408tert-Butyl [4-(4-hydroxyphenyl)butyl]carbamate

Product 1

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

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

Sources & evidence

ORD record
ord-8c41b7b58dbc4c638b2ff5b8a4f0dd10
Source dataset
uspto-grants-2008_08
Patent number
US07410968B2

Reaction notes

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