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

HRID 501679노트

반응식

HRID 501679 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9176b7cff35c410baa4f606736e5fa49
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772221B2

반응 노트

불러오는 중…