Allyl bromide → (R)-N-(2-(allyloxy)-1-phenylethyl)-2,2,2-trifluoroacetamide

HRID 501679Notes

Reaction equation

HRID 501679 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]([NH:5][C@H:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:7][OH:8])=[O:4].[Li][CH2:18][CH2:19][CH2:20]C.CN1C(=O)N(C)CCC1.C(Br)C=C>C1COCC1>[CH2:20]([O:8][CH2:7][C@H:6]([NH:5][C:3](=[O:4])[C:2]([F:15])([F:16])[F:1])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH:19]=[CH2:18]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 15653812(R)-2,2,2-Trifluoro-N-(2-hydroxy-1-phenylethyl)acetamideHCID 178418339Butyllithium

Product 1

HCID 86622318(R)-N-(2-(allyloxy)-1-phenylethyl)-2,2,2-trifluoroacetamideYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Step Q (2): (R)-2,2,2-Trifluoro-N-(2-hydroxy-1-phenylethyl)acetamide from step Q (1) (3.34 g, 14.3 mmol) was dissolved in THF (30 mL) and chilled to −78° C. n-BuLi (12 mL, 29 mmol, 2.5 M in hexanes) and DMPU (3.45 mL, 29 mmol) were added to the mixture. After 10 min, allyl bromide (12 mL, 143 mmol) was added. The mixture was warmed to rt and then heated to reflux for 16 h. The mixture was quenched with saturated NH4Cl, diluted with 1 N NaOH, and 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 2.88 g (73% yield) of (R)-N-(2-(allyloxy)-1-phenylethyl)-2,2,2-trifluoroacetamide as a yellow residue. LC-MS (M+H)+=274.06. 1H NMR (300 MHz, CDCl3) δ ppm 3.66-3.79 (m, 2H) 3.95-4.01 (m, 2H) 5.07-5.26 (m, 3H) 5.73-5.89 (m, 1H) 6.95-7.06 (m, 1H) 7.24-7.37 (m, 4H).

Workup

  1. additionwere added to the mixture
  2. temperatureheated
  3. temperatureto reflux for 16 h
  4. customThe mixture was quenched with saturated NH4Cl
  5. additiondiluted with 1 N NaOH
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by silica-gel column chromatography (0-25% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-9176b7cff35c410baa4f606736e5fa49
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…