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

HRID 2220986Notes

Reaction equation

HRID 2220986 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 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. 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 dichloromethane (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-edd1354fc89e4460a57839d05096eb7d
Source dataset
uspto-grants-2008_05
Patent number
US07368451B2

Reaction notes

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