Epichlorohydrin → 1-(3,4-Dichlorophenyl)-2-hydroxymethyl-cyclopropanecarbonitrile

HRID 332130

반응식

HRID 332130 반응식
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[C:5]#N.[NH2-:11].[Na+].[CH2:13]([CH:15]1[O:17][CH2:16]1)Cl.[Cl-:18].[NH4+].[CH2:20]1COCC1>>[Cl:18][C:2]1[CH:3]=[C:4]([C:5]2([C:20]#[N:11])[CH2:13][CH:15]2[CH2:16][OH:17])[CH:7]=[CH:8][C:9]=1[Cl:10]

참가 물질

6

반응물 5

HCID 7835EpichlorohydrinHCID 8028TetrahydrofuranHCID 24533Sodium amide2회HCID 25517Ammonium ChlorideHCID 810513,4-Dichlorobenzonitrile

생성물 1

HCID 248153691-(3,4-Dichlorophenyl)-2-hydroxymethyl-cyclopropanecarbonitrile

반응 조건

온도
-25 °C

실험 절차

To an oven-dried, three-necked, 500 mL round-bottomed flask was added the compound 3,4-dichlorobenzonitrile and THF with stirring under argon. The solution was cooled to −25° C. in a dry ice/MeCN bath and charged with 5.3 g of sodium amide. The resulting yellow suspension became orange upon stirring and was warmed to ambient temperature over 2 hours. The brown mixture was cooled to −25° C. and epichlorohydrin was added drop-wise over 10 minutes followed by a second equivalent of sodium amide in one portion. The golden brown mixture was stirred at −25° C. and warmed to 15° C. over 8 h. The dark red-colored mixture was poured (with stirring) into 500 mL of saturated ammonium chloride. The organic phase was separated and dried over magnesium sulfate for 12 h. The mixture was filtered and concentrated under reduced pressure and dried to afford 31 g of red oil. Half of the material was loaded onto a silica gel (250 g) column and eluted first with hexane. Later the polarity was increased to 10% EtOAc in hexanes and finally to 20% EtOAc in hexanes. Tubes containing the product were combined and concentrated, and dried under a high vacuum to give the product as a mixture of diastereomers. Yield: 6.8 g (42%); LCMS: (+) ESI: m/z=242 [M]+; 1H NMR (300 MHz, CDCl3, peaks corresponding to syn isomer listed) δ 7.43 (m, 2H, ArH), 7.7.14 (m, 1H, ArH), 4.09 (dd, 1H, CHOH, J=12 Hz and 4.8 Hz), 3.74 (dd, 1H, CHOH, J=12 Hz and 8.4 Hz), 2.73 (bs, 1H, OH), 1.91 (m, 1H, ArCCH2CH), 1.62 (m, 2H, ArCCH2CH).

후처리

  1. stirringupon stirring
  2. temperaturewas warmed to ambient temperature over 2 hours
  3. temperatureThe brown mixture was cooled to −25° C.
  4. stirringThe golden brown mixture was stirred at −25° C.
  5. temperaturewarmed to 15° C. over 8 h
  6. additionThe dark red-colored mixture was poured
  7. customThe organic phase was separated
  8. dry with materialdried over magnesium sulfate for 12 h
  9. filtrationThe mixture was filtered
  10. concentrationconcentrated under reduced pressure
  11. customdried

출처 및 근거

ORD 기록
ord-b5d392f4095f4a239c8d7d7b7101bad7
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877798B2

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