Iodoethane → 3-(3,4-Difluorophenyl)-1-ethylpyrrolidin-3-ol

HRID 1931814노트

반응식

HRID 1931814 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[K+].[K+].I[CH2:22][CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][N:11]([CH2:22][CH3:23])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

참가 물질

6

반응물 4

HCID 6340IodoethaneHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 635869723-(3,4-Difluorophenyl)pyrrolidin-3-ol

생성물 1

HCID 251436623-(3,4-Difluorophenyl)-1-ethylpyrrolidin-3-ol수율 39.6%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
80 °C

실험 절차

In a sealed tube a mixture of enantiomer E1 of 3-(3,4-difluorophenyl)pyrrolidin-3-ol (0.26 g, 1.3 mmol), acetonitrile (3 mL), potassium carbonate (0.269 g, 1.95 mmol) and iodoethane (0.20 g, 1.3 mmol) was heated under microwave irradiation at 80° C. for 25 minutes. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was washed with brine, dried (Na2SO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 35:65 to 50:50) gave the title compound (0.117 g). [α]D=+19.4° (methanol). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 136-137° C.; MS m/z (relative intensity, 70 eV) 227 (M+, 10), 207, (19), 141 (20), 72 (42), 71 (bp).

후처리

  1. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
  2. washthe combined organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customPurification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 35:65 to 50:50)

출처 및 근거

ORD 기록
ord-5ec5579c2add408180d4fd5cb0c26ce0
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188301B2

반응 노트

불러오는 중…