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

HRID 501683ノート

反応式

HRID 501683 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-47f0c0e4404b4ce6b25fd381b9f02e84
出典データセット
uspto-grants-2010_08
特許番号
US07772221B2

反応ノート

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