Allyl bromide → N-(3-(allyloxy)-1-(3-methoxyphenyl)propyl)-2,2,2-trifluoroacetamide

HRID 501683Notes

Reaction equation

HRID 501683 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([NH:5][CH:6]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1)[CH2:7][CH2:8][OH:9])=[O:4].[Li][CH2:21][CH2:22][CH2:23]C.CN1C(=O)N(C)CCC1.C(Br)C=C>C1COCC1>[CH2:23]([O:9][CH2:8][CH2:7][CH:6]([NH:5][C:3](=[O:4])[C:2]([F:18])([F:19])[F:1])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1)[CH:22]=[CH2:21]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 866223212,2,2-Trifluoro-N-(3-hydroxy-1-(3-methoxyphenyl)propyl)acetamideHCID 178418339Butyllithium

Product 1

HCID 86622320N-(3-(allyloxy)-1-(3-methoxyphenyl)propyl)-2,2,2-trifluoroacetamideYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Step R (2): 2,2,2-Trifluoro-N-(3-hydroxy-1-(3-methoxyphenyl)propyl)acetamide from step R (1) (1.99 g, 7.18 mmol) was dissolved in THF (20 mL) and chilled to −78° C. n-BuLi (5.76 mL, 14.4 mmol, 2.5 M in hexanes) and DMPU (1.73 mL, 14.4 mmol) were added and the resulting mixture was stirred for 45 min. Allyl bromide (3.04 mL, 36 mmol) was added. The mixture was warmed to rt and then heated to reflux for 3 days. The mixture was quenched with saturated NH4Cl. After 15 min, the mixture was diluted with 1 N NaOH and the aqueous mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica-gel column chromatography (0%-25% EtOAc/Hexanes) afforded 610 mg (27% yield) of N-(3-(allyloxy)-1-(3-methoxyphenyl)propyl)-2,2,2-trifluoroacetamide as a viscous yellow oil. LC-MS (M+H)+=318.37; 1H NMR (300 MHz, CDCl3) δ ppm 1.89-2.01 (m, 1H) 2.14-2.29 (m, 1H) 3.34-3.52 (m, 2H) 3.77 (s, 3H) 3.91 (d, J=5.86 Hz, 2H) 5.10-5.30 (m, 3H) 5.79-5.95 (m, 1H) 6.70-6.82 (m, 3H) 7.19-7.29 (m, 1H).

Workup

  1. additionwere added
  2. temperatureheated
  3. temperatureto reflux for 3 days
  4. customThe mixture was quenched with saturated NH4Cl
  5. waitAfter 15 min
  6. additionthe mixture was diluted with 1 N NaOH
  7. extractionthe aqueous mixture was extracted with EtOAc
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by silica-gel column chromatography (0%-25% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-47f0c0e4404b4ce6b25fd381b9f02e84
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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